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1616 Gut 1993; 34:1616-1621

Mechanism of 's inhibitory action on pancreatic enzyme secretion: modulation of Gut: first published as 10.1136/gut.34.11.1616 on 1 November 1993. Downloaded from transmission studies in vivo and in vitro

K-H Herzig, G Brunke, I Schon, M Schaffer, U R Folsch

Abstract , , y-amino butyric This study examined the inhibitory mechanism acid, , (CCK) and of galanin, a 29 polypeptide on .2'- The localisation and the coexis- pancreatic enzyme secretion in anaesthetised tence with these strongly sug- rats, isolated pancreatic acini, and lobules. gests that galanin plays an important part in the Urethane anaesthetised rats with pancreatic modulation of neural transmission. In the pan- fistulas pretreated with 3-0-methyl- creas galanin immunoreactive nerve fibres have glucopyranose (500 mg/kg/h) were stimulated been detected in several species, only the intra- with an intravenous bolus of 2-deoxyglu- pancreatic abundance and distribution varies cose (2-DG) (75 mg/kg). Maximal amylase slightly among them.9 In the rat galanin secretion was mean (SEM) 274 (19)% of basal immunoreactive nerve fibres are located around secretion. Atropine (150 ug/kg/h) and galanin blood vessels and scattered in the exocrine pan- (10 nmol/kg/h) almost completely inhibited creatic parenchyma, occasionally in the islets.8 In 2-DG stimulated amylase secretion suggesting the dog on the other hand, galanin an inhibition of cholinergic transmission. To immunoreactive nerves are most abundant in the further test this possibility this study investi- islets.6 Galanin immunoreactivity has not been gated the effect of galanin on carbachol and detected in the intrapancreatic of the cholecystokinin stimulated amylase release dog, therefore Dunning et al suggested an extrin- from isolated pancreatic acini. Galanin did not sic origin of the galanin immunoreactive nerves.

suppress carbachol or cholecystokinin stimu- In contrast with dogs, in the human pancreas http://gut.bmj.com/ lated amylase release, indicating that galanin galanin immunoreactive nerves are mainly dis- inhibits exocrine secretion by indirect mecha- tributed in the exocrine tissue including intra- nisms. The cholinergic pathway was assessed pancreatic ganglia.9 According to their results by using pancreatic lobules containing intra- Shimosegawa etal suggested an intrinsic origin of pancreatic neurons. Veratridine, a sodium galanin immunoreactivity and speculated that in channel activator, dose dependently stimu- the human pancreas galanin is a likely neuro-

lated amylase release. Veratridine (100 ,M) transmitter in the parasympathetic post- on October 2, 2021 by guest. Protected copyright. stimulated amylase release by 411 (10)% of ganglionic nerve system. basal secretion. Atropine (1 uM) or tetro- Mixed pancreatic nerve stimulation releases dotoxin (1 uM) almost completely blocked galanin into the venous effluent of dogs inhibi- veratridine stimulated amylase release. ting and secretion and mod- Galanin (1 uM) significantly inhibited vera- estly stimulating output.'0 In addition, tridine stimulated amylase release with a maxi- galanin has been shown to inhibit the secretion of mal inhibition of 50% (p<005). In addition, other gastrointestinal hormones, gut motility, when lobules were incubated with [3H]- and exocrine pancreatic secretion.31'12 The choline, galanin significantly (p<0-05) in- mechanism, however, through which galanin hibited veratridine stimulated release of newly acts to inhibit exocrine pancreatic secretion is synthesised [3H]-acetylcholine. Thus galanin unclear. In the brain and the myenteric plexus inhibits pancreatic secretion by inhibiting galanin has been shown to inhibit cholinergic cholinergic transmission. These studies show transmission. '5' On the other hand, galanin that galanin inhibits rat pancreatic enzyme weakly inhibited amylase release from isolated secretion by an indirect mechanism by reduc- rat pancreatic acini suggesting a direct effect on I Department of Internal Medicine, Christian- ing cholinergic transmission. the acini. 16 Albrechts-Universitat, (Gut 1993; 34: 1616-1621) Therefore, in this study we investigated the Kiel, Germany hypothesis that galanin inhibits pancreatic K-H Herzig G Brunke enzyme secretion by presynaptic modulation of I Schon Galanin, a 29 amino acid , was first acetylcholine release. To test this hypothesis we M Schaffer isolated from porcine intestinal mucosa by examined the effect of galanin (a) on 2-deoxy- U R Folsch Tatemoto et al using a method that detects its glucose (2-DG) stimulated amylase release in Correspondence to: Dr K-H Herzig, I Department C-terminal amide structure.' The name was anaesthetised rats, (b) on CCK8 and carbachol of Internal Medicine, derived from its N-terminal amino acid glycine stimulated amylase release from isolated pan- Christian-Albrechts- Universitat, Kiel, Germany. and the C-terminal amino acid alanine. Galanin is creatic acini devoid ofneural elements, (c) on the Accepted for publication widely distributed in the neurons of the central sodium channel activator veratridine stimulated 10 March 1993 nervous system and the gut and coexists with amylase release from pancreatic lobules contain- Inhibition ofpancreatic enzyme secretion 1617

ing neural elements, and (d) on veratridine Isolated pancreatic acini studies stimulated acetylcholine release. Isolated rat pancreatic acini were prepared by

collagenase digestion, as described previously, to Gut: first published as 10.1136/gut.34.11.1616 on 1 November 1993. Downloaded from test if galanin directly affects CCK or carbachol Materials and methods stimulated amylase release.2' Briefly, pancreatic tissue was incubated in 10 mM HEPES buffered MATERIALS Ringer solution (HR) containing 100 U/ml col- The following substances were purchased: tryp- lagenase, 6 mM glucose, 0-5% bovine serum sin (type II-S), soybean trypsin inhibitor (SBTI) albumin, 0-1% soybean trypsin inhibitor, and (type I-S), 2-deoxyglucose, 3-0-methylgluco- Eagle's minimum amino acid supplement; the pyranose, taurocholate, veratridine, tetro- digestion buffer was additionally injected into dotoxin, physostigmine, hemicholinium, atro- the pancreatic interstitium to permit better pine sulphate, urethane from Sigma Chemical digestion of tissue. After 30 minutes' incubation (Deisenhofen, Germany), N-2-hydroxy- at 37°C under 02 saturation in a shaking water ethylpiperazine-N'-2-ethanesulphonic acid bath, acini were dispersed with mild shearing (HEPES), bovine serum albumin (fraction V) forces, passed through a double filter gauze, and from E Merck (Darmstadt, Germany), col- purified by sedimentation in 4% bovine serum lagenase from Bayer Diagnostic (Miinchen, albumin. Acini were washed three times in HR Germany), minimal Eagle's amino acid supple- and added in aliquots to prepared vials contain- ment from Gibco/BRL (Life Technologie, Egg- ingCCK8 or carbachol in the presence or absence enstein, Germany), rat galanin from Peninsula of galanin (1 uM). The vials were incubated Laboratories (Heidelberg, Germany), and under 02 saturation at 37°C in a shaking water [methyl-3H] choline chloride from Amersham bath for 30 minutes. The reaction was stopped (Braunschweig, Germany). by placing the vials on ice and separating the cells by centrifugation. Amylase released into the medium and total acinar amylase content were METHODS measured. All experiments were done in tripli- cate and amylase released was expressed as a In vivopancreatic secretion studies percentage ofinitial total amylase content. Male starved Sprague-Dawley rats (Zentral- institut fur Versuchstierzucht, Hannover, Ger- many), weighing between 200-250 g, were Pancreatic lobule studies anaesthetised with urethane (1-3 g/kg body Pancreatic lobules containing postganglionic weight). Body temperature was maintained at neural elements and islets were prepared by the 38°C with a heating pad. The pancreas was method of Scheele and Palade.22 Briefly, the

exposed through a midline abdominal incision pancreas was removed and HR buffer solution http://gut.bmj.com/ and the common bile pancreatic duct was cannu- injected into the interstitium. Lobules were lated at the sphincter of oddi with a tapered excised with forceps and scissors. The lobules polyethylene tip attached to silastic tubing. A were washed and transferred into baskets with second cannula was placed into the , mesh bottoms allowing the buffer to drain but slightly above the sphincter for continuous infu- retain the lobules. The baskets were placed into sion of a trypsin bile acid solution (2 mg trypsin, temperature controlled chambers at 37°C under a

dissolved in 50 mmol/l NaHCO3, 78 ,mol/I constant drip (0 5 ml/min) of HR buffer. The on October 2, 2021 by guest. Protected copyright. sodium taurocholate, rate of infusion 1 ml/h). superfusion medium was collected under the This amount was sufficient to suppress CCK basket in small vials. After a 45 minute adjust- release. 7 For intravenous infusions a cannula was ment period in the chambers five 4 minute basal inserted into the external jugular vein and the collections were taken and the lobules were incisions covered with a moist gauze. stimulated with the sodium channel activator The diverted bile pancreatic juice was collected veratridine (10 ,uM-500 ,uM) for eight minutes.23 in small vials for 15 minute periods, the volume Veratridine has no effect on pancreatic determined, and amylase measured using an auto- acini24; it is known to depolarise existing cells by analyser (Eppendorf ACP 5040, Hamburg, blocking the inactivation ofNa+ channels.25 Each Germany) according to the method of Kruse- stimulation was followed by eight 4 minute Jarres et al.'8 After a two hour basal period, collection periods. In the different treatment atropine (150 ,4g/kg/h) or galanin (10 nmol/kg/h) groups atropine (1 ,M) or tetrodotoxin (1 ,uM), a was infused intravenously for the remainder ofthe specific sodium channel blocker, or galanin experiment; control rats received saline.'2 Thirty (1 ,M) was already added individually to the minutes after the start of galanin infusion, rats superfusion buffer 20 minutes before and were pretreated with 3-0-methylglucopyranose throughout the stimulation period. At the end of (500 mg/kg/h) for 30 minutes and stimulated with the experiment, the lobules were homogenised a bolus injection of 2-deoxyglucose (2-DG; 75 mg/ with a Wheaton-Dounce glass-glass homoge- kg).'9 2-DG stimulates pancreatic secretion by niser. Amylase content of the homogenates and cholinergic central stimulation caused by cyto- the superfusion medium was determined and glucopoenia in the nuclei ofthe solitary tract.20 3-0- results are expressed as a percentage of basal methylglucopyranose in addition to 2-DG is fractional release. Baseline secretion is expressed thought to aggravate the central cytoglucopoenia. 9 as 100%. After the bolus injection of 2-DG pancreatic secretion was measured for additional 120 minutes. Results were expressed as a percentage of Acetylcholine release studies basal amylase output. Acetylcholine release was measured by the 1618 Herzig, Brunke, Schon, Schaffer, Folsch

2-DG method described by Wu et al.26 Pancreatic lobules were depleted of endogenous acetyl-

300 - choline by electrical field stimulation. Platinum Gut: first published as 10.1136/gut.34.11.1616 on 1 November 1993. Downloaded from wires were attached to the bottom of a basket, which was placed into a heating chamber under a 0. constant drip. Pulses of 1 ms duration at 4 Hz at 0 40 volts were given for 15 minutes. The lobules a,) were incubated with 0-2 /,M [methyl-3H] choline U) 200 - co chloride in HR buffer containing 50 ,uM physo- E stigmine, a cholinesterase inhibitor, at 37°C for 45 minutes in a shaking incubator under 0, CU) saturation. Afterwards the lobules were washed .0 six times for 10 minutes and transferred into the 0 100 - baskets. Hemicholinium (10 was added to 71 ,uM) the buffer to prevent released acetylcholine being taken up again. The same perfusion system and experimental design as described above was used in the pancreatic lobule studies. Instead of 0 * w g | w s amylase measurement 1 ml of collected super- 0 15 30 60 90 fusion buffer was added to 9 ml of scintillation Time (min) fluid (Quickzint 2000; Zinser Analytic, Ger- many). The lobules were solubilised overnight in Figure 1: Effect ofatropine and galanin on 2-deoxyglucose (2-DG) stimulated amy, in anaesthetised rats. After a two hour basal period atropine (150 pglkglh) orgalani 'outPut 10% sodium dodecyl sulfate. Radioactivity was nmollkglh) were infused throughout the remainder ofthe experiment. Rats were pret ted counted in a Beckman LS-7800 scintillation with 3-0-methylglucopyranosefor 30 minutes before the bolus injection of2-DG (75 #kg). counter. Counts were expressed as a percentage 2-DG (a), 2-DG+atropine (o), 2-DG+galanin (0). Two way analysis ofvarian with of basal fractional release. Baseline secretion is repeated measures showed a significant inhibitory effect ofatropine and galanin over ne (F=8-7; p<005; df1/18); values are means ofeight experiments. expressed as 100%. Veratridine evoked [3H] efflux has been called [3H]-acetylcholine, because 30 - earlier studies showed that virtually all the -0 veratridine evoked release of [3H] activity from cUa)(n intrapancreatic cholinergic ganglia represents a)co ['H]-acetylcholine 2728

1.CL a-c 20 STATISTICS 0

Results are expressed as mean (SEM). Data were http://gut.bmj.com/ U1) CU analysed using analysis of variance with the 3- E method of Dunn for multiple contrasts or co0 Student's t test where appropriate. Statistical CU 0 10 significance was set at p<005. CU

Results on October 2, 2021 by guest. Protected copyright. 0 IN VIVO STUDIES 0 Basal -13 -12 -11 -10 -9 -8 Basal amylase output was monitored two hours before the start of galanin to ensure a CCK log (M) complete suppression of the negative feedback 30 1 B mechanism. 7 Basal amylase output averaged -0 a) 1544 U/h. Pretreatment with 3-0-methylgluco- pyranose (500 mg/kg/h) before the bolus injec- a) tion of 2-DG did not stimulate amylase output (data not shown). Bolus injection of 2-DG (75 a) - 274 C 20 mg/kg) raised amylase output by (19)% 0 within 45 minutes (Fig 1). Atropine a) u) (150 ,ug/kg/h) blocked the stimulatory effect of 2-DG completely proving that 2-DG acts by E cholinergic pathways to stimulate pancreatic enzyme secretion (Fig 1). Also galanin (10 nmol/ l10 0 kg/h) completely inhibited 2-DG-stimulated

-C amylase output suggesting that galanin might affect cholinergic transmission (Fig 1). -0 0

IN VITRO STUDIES 0 . - Basal -7 -6 -5 -4 Carbachol log (M) Isolated pancreatic acini studies In isolated pancreatic acini stimulation with Figure 2: Effect ofgalanin on cholecystokinin 8 (CCK8) (A) and carbachol (B) stimulated amylase release from isolated pancreatic acini. Control acini (0), acini treated with galanin various concentrations of CCK8 and carbachol (I ,M) (0). Values are means ofseven experiments. stimulated amylase release in the typical biphasic Inhibition ofpancreatic enzyme secretion 1619

a, 60 500 Un co or T7 Qa a)

a) 50 Gut: first published as 10.1136/gut.34.11.1616 on 1 November 1993. Downloaded from a, 'Or. 400 '0 .. co .....a > 4c)o .-.-.-.-.-.-.-.-.-.-.-. _i E ...... _ co ...... U 300 c"30)o ...... E*:-:-:-:-::-:-:-:-:-...... ~C... CO , J~ CO~~~~a 5x 10-4M ~ C X 2c )o ...... 0..-.-..-.-.-.-.-.-.- co 200 ., -T- ...... C ...... cn0 ... ~ co )o ...... C 5x104M...0 100

.... 0 ...... 10 --5 M 5 x 10-5 M 10-4 M 0 Veratridine 10-4 M 10-4 M veratridine Figure 3: Amylase release from pancreatic lobules containing veratridine + 10-6 M galanin neural elements in response to veratridine, a sodium channel Figure 5: Effect ofgalanin on veratridine stimulated amylase activator. Values are means ofat least six experiments. releasefrom pancreatic lobules. Values are means of II experiments. *p

tor veratridine (100 ,M) caused a 412 (10)% amylase release in anaesthetised rats - a stimulus http://gut.bmj.com/ stimulation of basal amylase release. Tetro- that is known to act by cholinergic pathways.920 dotoxin (1 ,tM), a specific sodium channel Yagci et al found that galanin potently inhibited blocker, abolished amylase secretion stimulated , , and cholecystokinin stimu- by the highest dose of veratridine used (Fig 4). lated pancreatic protein and amylase secretion in Atropine (1 uM) also blocked the effect of the anaesthetised rat."2 According to the study veratridine showing that veratridine stimulated from Yagci et al we used a maximal dose of

amylase release is mediated by a cholinergic galanin to test the effect on cholinergically stimu- on October 2, 2021 by guest. Protected copyright. pathway. Addition of galanin to the superfusion lated amylase secretion and did not perform buffer for 20 minutes caused a 50% inhibition of additional experiments with lower concentra- veratridine (100 ,uM) stimulated amylase release tions, because our aim was to further elucidate providing further evidence that galanin inhibits the inhibitory mechanism. cholinergic transmission (Fig 5). In isolated pancreatic acini galanin failed to To prove this hypothesis, we preincubated 200 r-

600 a) ...... T ...... a) 500 a) a) a) Cu Cn In 400 mE 100 I F 300 0 U, Cu 200 ., _ ~ ~~~~~~~~~.-.-.-.-.-.. -oo ~~~~~~~~in~ ...... 0- ......

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, 1| *::I -: : :-:::::::::::: -: -0: :: :-&: 0: : : 5 x 10--4 M veratridine 5 x 10 M veratridine 5 x10-4 M 10 6 MTTX 10 6 Matropine 6 veratridine + veratridine + veratridine + 10 M galanin Figure 4: Effect of atropine or tetrodotoxin (TTX) on Figure 6: Effect ofgalanin on veratridine stimulated 'H- veratridine stimulated amylase release Jrom pancreatic acetylcholine (H-ACH) releasefrom pancreatic lobules. lobules. Values are means of six experiments. *p

have any inhibitory action on CCK8 or carbachol glycaemia on pancreatic secretion are contradic- stimulated amylase release. By contrast with our tory.32 33

findings, Ahren et al reported a weak, but The results of this study fit into the general Gut: first published as 10.1136/gut.34.11.1616 on 1 November 1993. Downloaded from significant, inhibitory action on CCK8 and car- concept of pancreatic enzyme regulation. The bachol stimulated amylase release in isolated rat importance of the cholinergic nervous system pancreatic acini. 6 They used different concentra- during the intestinal phase of digestion has been tions of galanin (100 pM-100 nM) on amylase well reported.3 35 Adler et al showed in humans a secretion stimulated by a supramaximal dose of complete blockade ofmeal stimulated pancreatic CCK8 (10 nM) and a submaximal dose of car- enzyme secretion by atropine, while the potent bachol (10 AM). At 10 nM CCK they saw a 9-7 CCK antagonist loxiglumide caused (0 6)% stimulation of total amylase release. only a 60% inhibition. Inhibitory like Addition of galanin (100 nM) reduced amylase galanin, , pancreastatin, secretion to 8% only. Carbachol stimulated peptide YY, and Y modulate stim- amylase release by 13-5%; addition of galanin (1 ulated pancreatic secretion by reducing acetyl- nM) reduced stimulation to 11 25%. The inhibi- choline release.27283637 The results of this study tion by galanin seems to be rather weak. To see a show that galanin is a functional member of this direct effect of galanin, we tested the highest family. Although the exact significance ofgalanin concentration ofgalanin (1 ,uM) on various doses in the regulation of pancreatic enzyme secretion ofCCK8 and carbachol. Our acini were far more is currently unknown, the new powerful receptor responsive to CCK8 and carbachol with the antagonist M-15 will provide us with the tool to maximal secretion of 24 (1-3)% at (10 pM) and further elucidate the complex regulation of pan- 21-6 (1-7)% at (5 ,uM), respectively (see Fig 2). creatic enzyme secretion.38 Interestingly, in the study reported by Ahren In summary, this study has shown that galanin et al higher doses of galanin (for example, is a powerful inhibitor of pancreatic enzyme 100 nM v 10 or 1 nM) did not inhibit carbachol secretion. Galanin elicits its inhibitory action stimulated amylase release. To propose a direct indirectly, partly by inhibition of acetylcholine effect of galanin on pancreatic acini, specific release from intrapancreatic neurons. receptors must exist on the acinar cell as they have been found on hamster 1B cells and the This paper is dedicated to Professor Dr med G Paumgartner, Department of Medicine II, Klinikum Grosshadern, Ludwig- insulinoma cell line Rin m SF.2930 Higher concen- Maximilian-University, Munich, Germany, on the occasion of his tration of galanin should lead to a higher occu- 60th birthday. This investigation was supported in part by the Deutsche pancy ofpossible galanin receptors on the acinar Forschungsgemeinschaft (He 1965/1-1). The study was presented cells and therefore result in a greater inhibition of in part at the 93rd Annual Meeting of the American Gastro- enterology Association, 1992, in San Francisco, Ca. The authors amylase secretion. Overall, the weak inhibitory thank Cornelia Wilgus for excellent technical assistance. effect of galanin on pancreatic acini reported by

Ahren et al cannot account for the complete 1 Tatemoto K, Rokaeus A, Jornvall H, McDonald TJ, Mutt V. http://gut.bmj.com/ Galanin. A novel biologically active peptide from porcine inhibition of 2-DG stimulated amylase secretion intestine. FEBS Lett 1983; 164: 124-8. seen in vivo. It remains unclear if the reduced 2 Bauer FE. Galanin: Ein neues biologisch aktives gastro- intestinales Neuropeptid. Z Gastroenterol 1990; 28: 160-9. responsiveness of their acini accounts for the 3 Rattan S. Role ofgalanin in the gut. Gastroenterology 1991; 100: different findings in isolated pancreatic acini. 1762-8. 4 Ahren B, Lindskog S. Galanin and the regulation of islet Because there was not a direct effect ofgalanin hormone secretion. IntJ Pancreatol 1992; 11: 147-60. on pancreatic acini in our preparation we investi- 5 Crawley JN. Coexistence of and "classical" neurotransmitters: Functional interactions between galanin gated possible indirect mechanisms. Veratridine and acetylcholine. Ann NYAcad Sci 1990; 574: 233-45. on October 2, 2021 by guest. Protected copyright. dose dependently stimulated amylase release in 6 Dunning BE, Ahren B, Veith RC, Bottcher G, Sundler F, Taborsky GJ Jr. Galanin: a novel pancreatic neuropeptide. pancreatic lobules by depolarising neural Amj Physiol 1986; 251: E127-33. elements in the lobules, which was significantly 7 Messel T, Harling H, Bottcher G, Johnsen AH, Holst JJ. Galanin in the porcine pancreas. Regul Pept 1990; 28: inhibited by galanin. Proof that galanin indeed 161-76. inhibits cholinergic transmission from presyn- 8 Lindskog S, Ahren B, Dunning BE, Sundler F. Galanin- immunoreactive nerves in the mouse and rat pancreas. aptic cholinergic neurons was provided by the Cell Tissue Res 1991; 264: 363-8. [3H]-acetylcholine study. Galanin significantly 9 Shimosegawa T, Moriizumi S, Koizumi M, Kashimura J, Yanaihara N, Toyota T. Immunohistochemical demonstra- inhibited [3H]-acetylcholine release. These tion of galaninlike immunoreactive nerves in the human results provide direct evidence that galanin pancreas. Gastroenterology 1992; 102: 263-71. 10 Dunning BE, Taborsky GJ. Galanin release during pancreatic inhibits pancreatic enzyme secretion by inhibit- nerve stimulation is sufficient to influence islet function. ing presynaptic cholinergic transmission. AmJ Physiol 1989; 256: E191-8. 11 Bauer EF, Zintel A, Kenny MJ, Calder D, Ghatei MA, Bloom Because galanin did not completely block SR. Inhibitory effect of galanin on postprandial gastro- amylase release, it might be possible that addi- intestinal motility and gut hormone release in humans. Gastroenterology 1989; 97: 260-4. tional inhibitory mechanisms are responsible for 12 Yagci RV, Altekin N, Zacharia S, Coy DH, Ertan A, the full inhibitory action of this peptide. The Rossowski WJ. Galanin inhibits pancreatic amylase secre- tion in pentobarbital-anaesthetized rats. Regul Pept 1991; secretion of the islet hormones somatostatin, 34: 275-82. glucagon, and pancreatic polypeptide - all 13 Yau WM, Dorsett JA, Youther ML. Evidence for galanin as an inhibitory neuropeptide on myenteric cholinergic neurons in known inhibitors of exocrine pancreatic secre- the guinea pig small intestine. Neurosci Lett 1986; 72: 305-8. tion - are inhibited rather than stimulated by 14 Tamura K, Palmer JM, Wood JD. Galanin suppresses nico- tinic synaptic transmission in the myenteric plexus ofguinea galanin.4 On the other hand, insulin secretion is pig small intestine. EurJt Pharmnacol 1987; 136: 445-6. inhibited as well. A recent study showed that 15 Fisone G, Wu FC, Consolo 5, Nordstrom 0, Brynne N, Bartfai T, et al. Galanin inhibits acetyicholine release in the anti-insulin serum could block the postprandial ventral of the rat: Histochemical, autoradio- exocrine pancreatic secretion,3' yet the mecha- graphic, in vivo and in vitro studies. Proc NatlAcadSci USA 1987; 84: 7339-43. nism of insulin's action on pancreatic secretion iS 16 Ahren B,Andren-Sandberg A, Nilsson A. Galanin inhibits not known. A reduced insulin secretion could amylase secretion from isolated rat pancreatic acini. Pancreas 1988; 3: 559-62. account in part for the diminished exocrine 17 Folsch UR, Cantor P, Wilms HM, Schafmayer A, Becker HD, secretion in vivo, although the effects of hyper- Creutzfeldt W. Role of cholecystokinin in the negative Inhibition ofpancreatic enzyme secretion 1621

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