Action of Adenosine in Estrogen-Primed Nonpregnant Guinea Pig Myometrium: Characterization of the Smooth Muscle Receptor and Coupling to Phosphoinositide Metabolism1

The smooth muscle of guinea pig uterus is contracted by aden-osine in a manner consistent with the presence of a punne nucleoside receptor of the P1-A1 subtype that is uncoupled from adenylate cyclase. Here we investigate the signal transduction mechanism responsible for adenosine’s ability to contract uterine smooth muscle. The A1 adenosine receptor antagonist [3H]-8-cyclopentyl-1,3-dipropyl xanthine ([3H]CPX) bound reversibly to a large number (1 72 ± 25 fmol/mg of protein) of receptors in myometnal smooth muscle membranes from estrogen-primed virgin guinea pigs with an affinity (KD = 1.77 ± 0.21 nM) similar to that expected of [3H]CPX binding to both central and penph-eral A1 receptors. In the absence of the stable GTP analog, guanosine-5’-O-[3-thiotriphosphate], agonist competition of [3H] cPX binding resulted in a biphasic curve that was best fi