Studies on the stereoselectivity of the P2-purinoceptor.
ATP, 2-chloro-ATP, 2-methylthio-ATP, and their unnatural L-enantiomers, were synthesized and their effects tested on the guinea-pig taenia coli and urinary bladder, and the stimulated frog ventricle. The potent P2-purinoceptor agonists, 2-chloro-ATP and 2-methylthio-ATP were, respectively, 30 and 200 times more effective than ATP in relaxing the guinea-pig taenia, but approximately as effective as ATP in contracting the guinea-pig bladder and augmenting the force of contraction of the frog ventricle. A high degree of stereoselectivity was observed for relaxations of the guinea-pig taenia coli produced by the P2-purinoceptoragonists, and 2-methylthio-ATP was over 700 times more effective than its L-enantiomer. In contrast, stereoselectivity for contraction of the guinea-pig bladder was observed only at low concentrations with each pair of enantiomers, and a similar low stereoselectivity was displayed by the frog ventricle. These results show that P2-purinoceptors mediating inhibitory responses in the guinea-pig taenia coli can show a high degree of stereoselectivity, while P2-purinoceptors mediating excitatory responses in the guinea-pig bladder and in the frog ventricle show little stereoselectivity. The partial stereoselectivity of the P2-purinoceptor in smooth muscle contrasts with the absolute stereospecificity of P1-purinoceptors for adenosine on smooth muscle and autonomic nerve terminals and the absolute stereospecificity of the receptor for ADP on the human platelet.
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003106:Colon / Q000187:drug effects; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011894:Rana pipiens; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011983:Receptors, Purinergic; D013237:Stereoisomerism; D001743:Urinary Bladder / Q000187:drug effects
D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate