P2-Purinoceptor Mediated Inhibition of Adenylate Cyclase Activity

Abstract In 1972 Burnstock proposed that adenosine 5′-triphosphate (ATP) is the principal neurotransmitter in non-adrenergic, non-cholinergic nerves through an interaction with P,-purinergic receptors. In 1985 Burnstock and Kennedy suggested a subdivision of this class of receptors into a Pk- and a Pzy-subclass on the basis of rank order of potency of various ATP-analogues in pharmacological studies. The potency order on the Pa-purinoceptor is αβ-methyleneATP (AMP.CPP) = p,y- methyleneATP (AMP.PCP) < ATP = 2-methylthioATP (2MeSATP), whereas the potency order on the P-purinoceptor is 2MeSATP << ATP < AMP.CPP = AMP.PCP. Derivatization of ATF at various positions resulted in a more pronounced definition of the structure-activity requirements for both subtypes of the purinoceptor. The P-purinoceptor is rather tolerant to modifications at the ribose moiety and the phosphate chain and the activity of adenine modified analogues is not affected. On the P-purinoceptor the activity almost disappears when ribosemodi...