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1 Department of Anatomy & Developmental Biology and Centre for Neuroscience, Universiy College London Geoffrey Burnstock
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4 PURINERGIC SIGNALLING: HISTORICAL OVERVIEW AND CURRENT DEVELOPMENTS by Professor Geoffrey Burnstock Department of Anatomy & Developmental Biology and Centre for Neuroscience University College London Gower Street, London WC1E 6BT The potent action of purine nucleotides and nucleosides on the heart and vasculature was first recognized in 1929 by Drury and Szent-Gyorgyi. The 'purinergic nerve' hypothesis was proposed by Burnstock in 1972, with evidence to suggest that ATP was a neurotransmitter in non-adrenergic, non-cholinergic nerves supplying the intestine, urinary bladder and parts of the vascular system. Later it became evident that ATP was a co-transmitter with classical transmitters, peptides and nitric oxide in autonomic and sensory-motor nerves. In 1978, receptors to purines were shown to belong to two main subtypes, namely P1-purinoceptors, that are selective to adenosine, and P2-purinoceptors that are selective for ATP and ADP. Subsequently, subtypes of P1-purinoceptors into A1, A2a, A2b and A3 have been identified and, based largely on data obtained from expression cloning of P2-purinoceptors and from transduction mechanisms, Abbracchio and Burnstock (1994) have proposed a new basis for subclassification of purinoceptors into P2X1-7 subtypes of a ligand-gated cation family and P2Y1-8 subtypes of a G-protein coupled family. Purinergic control of local vascular tone includes: P2X1-purinoceptor mediated constriction of smooth muscle by ATP released as a co-transmitter from sympathetic perivascular nerves; endothelial P2Y1 and 2-purinoceptor mediated vasodilatation (via NO) by ATP and UTP released from endothelial cells during shear stress and hypoxia; P1-purinoceptor (A2 subtype) modulation of transmitter release by adenosine resulting from extracellular breakdown of ATP. Receptors for purines and pyrimidines have also been identified in many other cell types, including endocrine, exocrine, bone and glial cells. Current developments include studies of the long-term (trophic) actions of purines in development and regeneration, and the development of selective agonists and antagonists for therapeutic purposes.
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36 Surgical Research and Anatomical Pathology, Royal Children's Hospital Michael R. Hurley, John M. Hutson, C. W. Chow
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43 1 ) Ohkubo & Shibata, J. Dent. Res., 1997 in press. 2) Ohkubo & Kitarnura, J. Dent. Res., 1997 submitted. 3) Hume, J. Dent. Res., 62: , 1987
44 45. EFFECTS OF NO DONORS ON IONIC CURRENTS IN GUINEA-PIG ILEAL SMOOTH MUSCLE CELLS Seong-Chun KWON1, Se-Joong RIM2, Eun-Ju Kim1 and Bok Soon KANG1 Departments of Physiology1 and Internal Medicine2, Yonsei University College of Medicine Seoul , Korea Nitric oxide (NO) has been shown to be a mediator of nonadrenergic, non-cholinergic inhibitory neurotransmission in intestinal smooth muscles. It has been suggested that NO donors susch as sodium nitroprusside (SNP) produces relaxation of smooth muscle via activation of guanylate cyclase and elevation of cgmp levels. We have therefore investigated the effects of NO, using SNP, on ionic currents in guinea-pig ileum. Conventional whole cell patch clamp technique was used to record the ionic currents. Outward potassium currents were activated by step pulses which were held at -60 mv. Depolarization-activated currents. SNP also decreased the inward Ca2+ current which is activated by application of step pulses. These results suggest that SNP-induced inhibitory effect may be mediated by cgmp and these effects are related to the direct inhibition of Ca2+ currents and the activation of K+ currents.
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