Jpn. J. Pharmacol. 80 (4), 311 - 317 (1999)

Cross Desensitizations on Contractions by P2-Agonistsof of Guinea Pig Ileum

Chiemi Sato (1), Yasumi Tsujioka (2) and Takeshi Katsuragi (2,*)

(1) Research Laboratory of Biodynamics, (2) Department of Pharmacology, School of Medicine, Fukuoka University, Fukuoka 814 - 0180, Japan
(*) To whom correspondence should be addressed.

Abstract: The present study was designed to clarify the characteristics of contractions of guinea pig ileal longitudinal muscles evoked by ,-methylene ATP as compared with those by other P2-agonists. ,-Methylene ATP, ADP--S and 2-methylthio ATP as P2-agonists produced remarkable phasic contractions of the segment in a suramin-sensitive- and reactive blue-2-insensitive manner. However, ADP--S and 2-methylthio ATP, unlike ,-methylene ATP, showed a biphasic contraction accompanied by a second sustained phase. Their second sustained contractions were notably suppressed by 30 M reactive blue-2, probably being a component mediated by P2Y-purinoceptor. The phasic contractile response to ,-methylene ATP, but not ADP--S and 2-methylthio ATP, was largely reduced by tetrodotoxin and atropine, indicating that the contraction is due to acetylcholine released from the cholinergic nerves. At 100 M, ,-methylene ATP inhibited the phasic contractions caused by a low concentration of itself, but not those induced by ADP--S and 2-methylthio ATP, presumably serving as a desensitizer of the P2-receptor. Although ,-methylene ATP per se showed little contraction, it prevented the contraction evoked by ,-methylene ATP, but not those by ADP--S and 2-methylthio ATP. The contraction evoked by 100 M 2-methylthio ATP was attenuated in the presence of ADP--S at 10 and 30 M. From separate cross-interactions between two groups of P2-agonists, there seems to be different subtypes of P2X-purinoceptors in the pre- and postsynapse in producing phasic contractions, but not sustained contractions that are mediated by, presumably, the P2Y-purinoceptor of the ileum.

Keywords: Contraction, ,-Methylene ATP, ,-Methylene ATP, ADP--S, Guinea pig ileum

Copyright The Japanese Pharmacological Society 1999

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