Characterization of P2x-receptors in Rabbit Isolated Ear Artery

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1990 Nov 1

PMID 2076482

Citations 24

Authors

S E OConnor

B E Wood

P Leff

Affiliations

Soon will be listed here.

Abstract

1. The isolated central ear artery of the rabbit contracts in response to adenosine 5'-triphosphate (ATP) and analogues, effects proposed to be mediated by stimulation of P2x-receptors. We have extended the characterization of the purinoceptor in this tissue by examining the effects of a series of receptor agonists. The study was designed in such a way as to avoid factors which normally limit attempts to classify receptors on the basis of agonist potency orders. 2. D-alpha, beta-methylene ATP (D-alpha, beta-meATP), D-beta, gamma-methylene ATP (D-beta, gamma-meATP), L-beta, gamma-methylene ATP (L-beta, gamma-meATP), 2-methylthio-D-ATP (2-MeSATP) and ATP produced concentration-related contractions of the ear artery with similar maximum responses, suggesting that they were full agonists. Selective desensitization of P2x-receptors abolished or greatly reduced responses to D-alpha, beta-meATP, L-beta, gamma-meATP, D-beta, gamma-meATP. Responses to ATP were inhibited by by desensitization but a significant resistant component was still apparent. 3. D-alpha, beta-meATP was the most potent agonist tested (pA50 6.47 +/- 0.04) being 2138 times more potent than ATP and approximately 9 times more potent than L-beta, gamma-meATP. The agonist potency order was: D-alpha, beta-meATP greater than L-beta, gamma-meATP greater than D-beta, gamma-meATP greater than or equal to 2-MeSATP greater than ATP. This is generally consistent with the order proposed for P2x-receptors. The relative potencies of P2x-agonists in the rabbit ear artery show both similarities to and differences from data obtained in other smooth muscle preparations.

Citing Articles

Physiological significance of P2X receptor-mediated vasoconstriction in five different types of arteries in rats.

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Pharmacology of P2X channels.

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Regional variation in P2 receptor expression in the rat pulmonary arterial circulation.

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New insights on P2X purinoceptors.

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References

Cusack N, Hourani S, Loizou G, Welford L . Pharmacological effects of isopolar phosphonate analogues of ATP on P2-purinoceptors in guinea-pig taenia coli and urinary bladder. Br J Pharmacol. 1987; 90(4):791-5. PMC: 1917197. DOI: 10.1111/j.1476-5381.1987.tb11233.x. View

Burnstock G, Warland J . P2-purinoceptors of two subtypes in the rabbit mesenteric artery: reactive blue 2 selectively inhibits responses mediated via the P2y-but not the P2x-purinoceptor. Br J Pharmacol. 1987; 90(2):383-91. PMC: 1916939. DOI: 10.1111/j.1476-5381.1987.tb08968.x. View

von Kugelgen I, Haussinger D, Starke K . Evidence for a vasoconstriction-mediating receptor for UTP, distinct from the P2 purinoceptor, in rabbit ear artery. Naunyn Schmiedebergs Arch Pharmacol. 1987; 336(5):556-60. DOI: 10.1007/BF00169313. View

Liu S, McCormack D, Evans T, Barnes P . Evidence for two P2-purinoceptor subtypes in human small pulmonary arteries. Br J Pharmacol. 1989; 98(3):1014-20. PMC: 1854747. DOI: 10.1111/j.1476-5381.1989.tb14633.x. View

Wood B, Squire A, OConnor S, Leff P . ADP-beta-F is not a selective P2y-receptor agonist in rabbit jugular vein. Br J Pharmacol. 1989; 98 Suppl:794P. View

Potvin W, Varma D . Refractoriness of the gravid rat uterus to tocolytic and biochemical effects of atrial natriuretic peptide. Br J Pharmacol. 1990; 100(2):341-7. PMC: 1917439. DOI: 10.1111/j.1476-5381.1990.tb15806.x. View

Fedan J, Hogaboom G, Westfall D, Odonnell J . Comparison of contractions of the smooth muscle of the guinea-pig vas deferens induced by ATP and related nucleotides. Eur J Pharmacol. 1982; 81(2):193-204. DOI: 10.1016/0014-2999(82)90437-x. View

Kasakov L, Burnstock G . The use of the slowly degradable analog, alpha, beta-methylene ATP, to produce desensitisation of the P2-purinoceptor: effect on non-adrenergic, non-cholinergic responses of the guinea-pig urinary bladder. Eur J Pharmacol. 1982; 86(2):291-4. DOI: 10.1016/0014-2999(82)90330-2. View

Cusack N, Hourani S . Some pharmacological and biochemical interactions of the enantiomers of adenylyl 5'-(beta, gamma-methylene)-diphosphonate with the guinea-pig urinary bladder. Br J Pharmacol. 1984; 82(1):155-9. PMC: 1987245. DOI: 10.1111/j.1476-5381.1984.tb16453.x. View

10.

Gustafsson L . Adenosine antagonism and related effects of theophylline derivatives in guinea pig ileum longitudinal muscle. Acta Physiol Scand. 1984; 122(2):191-8. DOI: 10.1111/j.1748-1716.1984.tb07498.x. View

11.

Kennedy C, Burnstock G . ATP produces vasodilation via P1 purinoceptors and vasoconstriction via P2 purinoceptors in the isolated rabbit central ear artery. Blood Vessels. 1985; 22(3):145-55. DOI: 10.1159/000158592. View

12.

Burnstock G, Kennedy C . Is there a basis for distinguishing two types of P2-purinoceptor?. Gen Pharmacol. 1985; 16(5):433-40. DOI: 10.1016/0306-3623(85)90001-1. View

13.

White T, Chaudhry A, VOHRA M, Webb D, Leslie R . Characteristics of P2 (nucleotide) receptors mediating contraction and relaxation of rat aortic strips: possible physiological relevance. Eur J Pharmacol. 1985; 118(1-2):37-44. DOI: 10.1016/0014-2999(85)90660-0. View

14.

Gordon J . Extracellular ATP: effects, sources and fate. Biochem J. 1986; 233(2):309-19. PMC: 1153029. DOI: 10.1042/bj2330309. View

15.

Kennedy C, Saville V, Burnstock G . The contributions of noradrenaline and ATP to the responses of the rabbit central ear artery to sympathetic nerve stimulation depend on the parameters of stimulation. Eur J Pharmacol. 1986; 122(3):291-300. DOI: 10.1016/0014-2999(86)90409-7. View

16.

Hourani S, Loizou G, Cusack N . Pharmacological effects of L-AMP-PCP on ATP receptors in smooth muscle. Eur J Pharmacol. 1986; 131(1):99-103. DOI: 10.1016/0014-2999(86)90521-2. View

17.

Reilly W, Burnstock G . The effect of ATP analogues on the spontaneous electrical and mechanical activity of rat portal vein longitudinal muscle. Eur J Pharmacol. 1987; 138(3):319-25. DOI: 10.1016/0014-2999(87)90469-9. View