Binding of [3H]oxytocin to purified myometrial plasma membranes was unaffected by continuous infusion of bradykinin over 5 days in rats pretreated with oestradiol 2 days before collection of tissue. In contrast, oxytocin treatment resulted in a 76% decrease in maximal binding of [3H]oxytocin and thereby in oxytocin receptor concentration without affecting the dissociation constant. The KM value (molar concentration giving half maximal contraction) of isolated uterine strips stimulated with oxytocin was increased and maximal contractile responses were reduced following oxytocin infusions.
The binding of [3H]bradykinin to purified plasma membranes was influenced by treatment with both oxytocin and bradykinin. Bradykinin infusions down-regulated the bradykinin receptor concentration by 19%, while the receptor affinity remained unchanged. Maximal contraction (Emax) values of isolated strips stimulated with bradykinin exhibited a slightly attenuated response and KM values were significantly enhanced. Long-term treatment with oxytocin down-regulated myometrial bradykinin receptors by 31%. In addition, oxytocin infusions caused Emax to decrease and KM to increase in experiments with isolated uterine strips stimulated with bradykinin.
It is concluded that the down-regulation of oxytocin and bradykinin receptors following prolonged exposure to oxytocin may result from changes in a common pathway for intracellular peptide receptor processing. Likewise, the increased KM values of isolated myometrial strips (despite unchanged dissociation constants) suggest that prolonged oxytocin treatment affects the coupling between receptor activation and contractile response.