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 ƒ¿,ƒÀ-methylene ATP as compared with those by other P2-agonists. ƒ¿,ƒÀ-Methylene ATP, ADP-ƒÀ-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-ƒÀ-S and 2-methylthio ATP, unlike ƒ¿,ƒÀ-methylene ATP, showed a biphasic contraction accompanied by a second sustained phase. Their second sustained contractions were notably suppressed by 30 ƒÊM reactive blue-2, probably being a component mediated by P2Y-purinoceptor. The phasic contractile response to ƒ¿,ƒÀ-methylene ATP, but not ADP-ƒÀ-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 ƒÊM, ƒ¿,ƒÀ-methylene ATP inhibited the phasic contractions caused by a low concentration of itself, but not those induced by ADP-ƒÀ-S and 2-methylthio ATP, presumably serving as a desensitizer of the P2-receptor. Although ƒÀ,ƒÁ-methylene ATP per se showed little contraction, it prevented the contraction evoked by ƒ¿,ƒÀ-methylene ATP, but not those by ADP-ƒÀ-S and 2-methylthio ATP. The contraction evoked by 100 ƒÊM 2-methylthio ATP was attenuated in the presence of ADP-ƒÀ-S at 10 and 30 ƒÊM. 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, ƒ¿,ƒÀ-Methylene ATP, ƒÀ,ƒÁ-Methylene ATP, ADP-ƒÀ-S, Guinea pig ileum