Cross Desensitizations on Contractions by P2-Agonists of Guinea Pig Ileum
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The present study was designed to clarify the characteristics of contractions of guinea pig ileal longitudinal muscles evoked by α, β-methylene ATP as compared with those by other P2-agonists. α, β-Methylene ATP, ADP-β-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-β-S and 2-methylthio ATP, unlike α, β-methylene ATP, showed a biphasic contraction accompanied by a second sustained phase. Their second sustained contractions were notably suppressed by 30 μM reactive blue-2, probably being a component mediated by P2Y-purinoceptor. The phasic contractile response to α, β-methylene ATP, but not ADP-β-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 μM, α, β-methylene ATP inhibited the phasic contractions caused by a low concentration of itself, but not those induced by ADP-β-S and 2-methylthio ATP, presumably serving as a desensitizer of the P2-receptor. Although β, γ-methylene ATP per se showed little contraction, it prevented the contraction evoked by α, β-methylene ATP, but not those by ADP-β-S and 2-methylthio ATP. The contraction evoked by 100 μM 2-methylthio ATP was attenuated in the presence of ADP-β-S at 10 and 30 μM. 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.
- The Japanese Journal of Pharmacology
The Japanese Journal of Pharmacology 80(4), 311-317, 1999-08-01
The Japanese Pharmacological Society