CC/NUMBER 40 This Week’s Citation Classic ~ OCTOBER 1, 1990 Burnstock G. A basis for distinguishing two types of purinergic receptor. (Straub R W & Sods L. eds.) Ce/I membrane receptors for drugs andItormones: a multidisciplinary approach. New York: Raven Press. 1978. p. 107-18. [Department of Anatomy and Embryology, University College London. England]

This paperwas the tirst to distinguish two major subclass- after I proposed this division of purinoceptors, a es of receptor for extracellular purine nucleosides and cartoon appeared in my laboratory (see below), I nucleotides. Thesesubstances were known to have potent suspect drawn by Ian Mackenzie, showing healthy actions since the seminal studies of Drury and Szent- scepticism for my new hypothesis, and another was GyOrgyi in t929.t The subclassification into P~-and p, sent by my old colleague David Satchell from Mel- purinoceptors was based on the relative potency of ATP, bourne. ADP, AMP, and adenosine; the effectiveness of methyl- Nevertheless, in the years that followed, this das- xanthines as antagonists: and mediation or not by adenyl- sification was accepted by most laboratories, and ate cyclase. This recognition of distinct receptors for subdivisions of both P - and Pa-purinoceptors have adenosine and AlP was a trigger ior considerable expan- now been proposed; Ai1 and A subclasses of the Pi- sion of the field and resolved many of the earlier am- 2 purinoceptors~4and Pzx and P2y subclasses of the biguities. The Sd® indicates that this chapter has been Prpurinoceptor No less than 10 books have been cited in over 400 publications.1 published on purinoceptors in recent years (for ex- —~ ample, references 5 and 6). Several meetings and Purinergic Receptors—Subclassification symposia have been devoted to this subject, and I was invited to deliver the Ariëns Lecture on and Physiological Roles 4. “Purinergic Receptors” in 1987 in Gent and was Geoffrey Burnstock given an award for my contribution to “The Con- Department of Anatomy and cept of Purinergic Transmission” at the meeting Developmental Biology and held in Bethesda, Maryland, September 1989, on Centre for Neuroscience “Purine Nucleosides and Nucleotides in Cell Sig- University College London nalling: Targets for New Drugs” I was also asked to London WC1 E6BT present the opening overview at a meeting held in England Philadelphia, November 1989, on “Biological Ac- June 5, 1990 tions of Extracellular ATP/’ sponsored by the New York Academy of Sciences, and at the 4th Interna- Purinergic receptors were implicit in the puriner- tional. Symposium on Adenosine and Adenine gic hypothesis that I proposed in 1972,2 which sug- Nucleotides held at Lake Yamanaka, Japan, May gested that nonadrenergic, noncholinergic (termed 13-17, 1990. “purinergic”) nerves supplying the smooth muscle Currently particular interest is being shown by of the gut and bladder utilise a purine nucleotide as both dinicians and the drug industry in the the principal neurotransmitter. Thus I was asked by therapeutic potential of purinoceptor agonists and my old friends Ralph Straub and Liliana Boils to antagonists, especially for cardiovascular diseases, present a paper on “purinergic receptors” at the for abnormalities in urinary and respiratory sys- meeting they were organising in Crans-sur-Sierre, tems, and in behavioural disorders. Switzerland, june 1977, which was entitled “Drugs, Hormones and Membranes.” This was a trigger for me to make a thorough analysis of the literature on the actions ofadenyl compounds on a wide range of tissues. I remember running into my laboratory at PURINAL University College London, trailing a huge, elon- gated table to declare to my group that I had spotted a pattern to the actions of adenyl com- pounds and believed that there was a clear distinc- tion between receptors for adenosine and AMP or the one hand and ATP/ADP on the other. Some 0 the hints for this subdivision came from experi- ments on smooth muscle in our own laboratory, such as the distinct separation of ATP/ADP from AMP/adenosine in the dose-response curves of in- testinal smooth muscle and the opposite excitatory or inhibitory actions of ATP and adenosine, respec- tively, in the bladder. There were also reports of the differential effects of these purines in other tissues, such as brain, pancreas, liver, and blood cells. Soon

I. Drury A N & Szeni.G~orgyiA. The physiological activity of adenine cotnpounds with especial reference to their action upon the mammalian hcart. I. Phvsiol.—London 68:213-37. 929. (Cited 485 times since 945.) 2. Burnsiock G. Purinergic nerves. Pharmucol. Re”. 24:509-81, 972. (Cited 1.135 times.) ISee also: Burnstock G. Citation Classic. Current Contents/Life Sciences 28(3):ts. 21 January 985.1 3. Ribeiro J A. Adenosine receptors in the nervous system. London: Taylor & Francis, 1989, 4. Burostock G & Kennedy C. Is there a basis for disttnguishing two types of purinoccptor? Ceo Pharmacol 16:433-40. 985. ICited ISO tinres.l 5. Burnstock 6, ed. Purinergtc receptorn. London: Chupman & Halt. 1981. 365 p. 6. Jacobson K, DalyJ & %langaniello V. eds. Purines ‘n cellular signalling: targets/or new drugs. New York: Springer-verlag. 1990,

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