Mechanism of Stimulant Effect of Acetylcholine in Isolated Frog Heart

Ind.

Pharmaceuticals Inc., New York, Jy of oxymorphone and Siquil- MECHANISM OF STIMULANT EFFECT OF ACETYLCHOLI E IN ISOLATED FROG HEART

A. W. BHAGWAT, S. S. RAO AND S. S. GUPTA esthesia. Acta Anaesth. Scandinav., 11: d and tissue levels of ether, chlorofonn, Department of Pharmacology, Gandhi Medical College, Bhopal 106, 1962. eralAnaesthetic Combinations for their o the Punjab Agricultural University, Summary: The mechanism of stimulant effect of acetylcholine has been investigated in atropinised isolated frog heart. The effect is reproducible and is not blocked by hexamethonium but is blocked by .,31: 316-318, 1959. dichloroisoprenaline, It persists after reserpine treatment and is increased after noradrenaline injection nical Laboratory Methods and Diagno- in such hearts. The mechanism of this effect thus appears to be a dual one, being partly mediated latile anaesthetic agent. Vet. Rec., 69: through the release of noradrenaline. Key Words: acetylcholine atropine hexamethonium dichloroisoprenaline nicotine esia on sheep. Am. J. Very. Res. 29: cardiac stimulant effect Rec., 72: 617-619, 1960. e anaesthesia in horses, effect on blood 1968. u TRODUCTIO , H. Popper and S. Samdes. Fulminant J. Med., 279 : 798-801, 1968. Isolated rabbit auricles brought to a standstill by quinidine, start contracting again d chloroform anaesthesia on the equine whenexposed to small concentrations of acetylcholine (2).. Similarly, in atropinised frog nd the evaluation of premedication. heart,acetylcholine produces tachycardia which is blocked 'by ganglion blocking agents (3,6). Thecardiac stimulant effect of acetylcholine in atropinised preparations has been attributed tosympathetic ganglionic stimulation or a direct release of noradrenaline from the sympathetic nerveendings (5). However, although the para sympathetic ganglia are known to exist in the frogheart, the presence of sympathetic ganglia or similar tissue is uncertain (4). In the present paper, the mechanism of the stimulant effect of acetylcholine has been studied in frog heart.

MATERIALS A D METHODS

Isolated frog heart was set up according to the technique of Bulbring (1) and was perfusedwith frog Ringer solution. The contractions were recorded with Starling heart lever. Thedrugs used were: acetylcholine ( 1 x 10":7 to \ I'x '10-5g); atropine sulphate (1 X 10-6 g); nicotine(5 X 10-6 g) and reserpine (0.5 mg/100 g im for 2 days).

RESULTS AND DISCUSSION

Acetylcholine alone caused cardiac inhibition in all the 12 preparations tested. After atropine perfusiou acetylcholine caused cardiac stimulation (Fig. 1) in 7 preparations while in the remaining 5 preparations cardiac stimulation was not produced even after increasing theconcentrations of atropine and acetylcholine. The cardiac stimulant effect was reprodu- 160 Bhagwat et al. olume 16 umber 2 cible after repeate perfusion but was reserpine the card hearts could be effect of nicotine effect of acety1cb The experil partly mediated ganglion like stD of acetylcholine . . reserpine treat AA AAAAA" A A ;"·A· involved in thii M_ H~ o~

.. 1. Burn, J.H. Fig. 1: Effect of acetylcholine (A at dots) (I) before, (ll) after atropine perfusion (At 1 x 10-6 g), (lIl)after atrop 2. Briscoe, S. and hexamethonium perfusion (H 1 x 10-6 g) and (IV) after DCI perfusion (D 1 x 10-6 g). Atrop- perfusion continued during IV. 3. Barlow, E. phia & LOll 4. Evans, C.L. S. Goodman, New York, 6. Heymans, (

Fig. 2 : Effect of acetylcholine ·..(A dots) and nicotine (N at d in perfused heart of frogt ted with reserpine (0.5 100 g im for 2 days). atropine perfusion (1xlO-I Upper record shows I effects before the adminis tion of noradrenaline lower record shows I increase in cardiac stimul effect of acetylcholine afl prior administration noradrenaline (NA at do lume16 Cardiac Stimulant Effect of Acetylcholine 161 umba 2 ible after repeated administration of acetylcholine and was not blocked by hexamethonium rfusionbut was blocked by DCI in all the 7 preparations (Fig. 1). In hearts treated with .rpine the cardiac stimulant effect of acetylcholine though less than in non-reserpinised rtscould be elicited in all the preparations (3 experiments) tested. The cardiac stimulant effectof nicotine was reduced or absent in these preparations. In these hearts the stimulant dT~ctof acetylcholine increased after prior treatment with noradrenaline (Fig. 2).

The experiments indicate that the stimulant effect of acetylcholine in atropinised heart is Jrtlymediated through the release of noradrenaline and could not be due to stimulation of pnglionlike structure. Further, the absence of tachyphylaxis after repeated administration facetylcholine in atropinised hearts and the persistence of small but significant effect ana reserpinetreatment suggest that the release of noradrenaline may not be the only mechanism A •. A . ml'Olvedin this effect. 0-+ REFERENCES • I. Burn,J.H. Practical Pharmacology. Blackwell Scientific Publications. Oxford, 1952, P. 30. perfusion(At.1 x 10-6 g), (III)after atropine DCI perfusion (D 1 x 10-6 g). Atropine ~. Briscoe,S. and J.H. Burn. Quinidine and acetylcholine. Br. J. Pharmac., 9: 42-45, 1954. J. Barlow, E. Cholinergic agents: In A Mannual of Pharmacology. ed. Sollmann, T. W.B. Saunders Co. Philadel- phia & London, 1957, P.415. 4. Evans,C.L. and H. Hartridge. Principles of Human Physiology, J. & A. Churchill Ltd. London 1956, P. 556. 5. Goodman, L.S. and A. Gilman, The Pharmacological Basis of Therapeutics. The MacMillan Company: New York, 1970, P. 468 . . Heyrnans,C. and C. Bennati. Acetylcholine. Arch. Int.Pharmacodyn. Ther., 79: 486-489,1949.

Fig. 2 : Effect of .acetylcholine '. (A at dots) and nicotine (N at' dots) In perfused heart of frog treated with reserpine (0.5 mgf 100 g. im for .2 days). At atropine perfusion (1x10-a g) Upper record shows the effects before the administra_ tion of noradrenaline and lower record shows the Increase III cardiac stimulant effect of acetylcholine after prior administration of noradrenaline (NA at dots).