title: Cross desensitizations on contractions by P2-agonists of guinea pig ileum.
abstract: The present study was designed to clarify the characteristics of contractions of guinea pig ileal longitudinal muscles evoked by alpha,beta-methylene ATP as compared with those by other P2-agonists. alpha,beta-Methylene ATP, ADP-beta-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-beta-S and 2-methylthio ATP, unlike alpha,beta-methylene ATP, showed a biphasic contraction accompanied by a second sustained phase. Their second sustained contractions were notably suppressed by 30 microM reactive blue-2, probably being a component mediated by P2Y-purinoceptor. The phasic contractile response to alpha,beta-methylene ATP, but not ADP-beta-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 microM, alpha,beta-methylene ATP inhibited the phasic contractions caused by a low concentration of itself, but not those induced by ADP-beta-S and 2-methylthio ATP, presumably serving as a desensitizer of the P2-receptor. Although beta,gamma-methylene ATP per se showed little contraction, it prevented the contraction evoked by alpha,beta-methylene ATP, but not those by ADP-beta-S and 2-methylthio ATP. The contraction evoked by 100 microM 2-methylthio ATP was attenuated in the presence of ADP-beta-S at 10 and 30 microM. 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.
authors.affiliation: Research Laboratory of Biodynamics, School of Medicine, Fukuoka University, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Tsujioka
authors.forename: T
authors.initials: T
authors.lastname: Katsuragi
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D018048:Receptors, Purinergic P2 / Q000145:classification / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D018048:Receptors, Purinergic P2; D013779:Tetrodotoxin; D013498:Suramin; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate