Regulation of guinea pig myometrial beta-adrenoreceptors by guanosine triphosphate and magnesium ion.

The effects of guanosine triphosphate (GTP) and magnesium on the interaction of 1-isoproterenol with beta-adrenoreceptors were studied in myometrial membranes from nonpregnant and late-pregnant (0.9 gestation, term 65 days) guinea pigs. The affinity of the beta-adrenoreceptor for 1-isoproterenol, as measured by inhibition of (-)125I-cyanopindolol binding, was increased by 10 mM MgCl2. The addition of 250 microM GTP reversed this process. In the presence of MgCl2, the competition curves could be resolved into two affinity states of the beta-adrenoreceptor, high and low, respectively. The ratio of the dissociation constant of the high-affinity state to that of the low-affinity state was significantly higher in late-pregnant than in the nonpregnant animals. In the presence of GTP, there was only one (low-affinity) state of the receptor detectable. In both groups of animals, the interaction between beta-adrenoreceptor agonists and myometrial beta-adrenoreceptors was positively modulated by MgCl2. This process was reversed by GTP. However, there appeared to be a differential regulation of the ability of the myometrial beta-adrenoreceptor to form a high-affinity state, depending on the reproductive state of the animal.