EFFECTS OF ADRENALINE AND NORADRENALINE IN SEPARATED LONGITUDINAL AND CIRCULAR MYOMETRIAL PREPARATIONS FROM THE GUINEA‐PIG: SELECTIVE MODULATION BY OVARIAN STEROIDS

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Abstract
Field-stimulated strips of circular and longitudinal myometrium from virgin adult guinea pigs were used to study the influence of ovarian steroids upon uterine responses to adrenaline [epinephrine] and noradrenaline [norepinephrine]. Preparations were taken from animals; untreated, on day 9 or 10 of the estrous cycle; treated for 14 days with estradiol cypionate, beginning on day 9 or 10; and treated for estradiol cypionate for 14 days, beginning on day 9 or 10, then given both estradiol cypionate and progesterone for a further four days. Estradiol treatment led to a 2-fold increase in the circulating level of progesterone; subsequent treatment of estradiol-primed animals with progesterone resulted in even higher circulating progesterone levels, comparable with those occurring during mid-pregnancy in this species. Both adrenaline and noradrenaline produced phentolamine-sensitive motor responses of circular myometrial preparations from each treatment group. Steroid treatment was without significant effect on the potencies or maximal effects of the 2 amines on the circular muscle layer. Both catecholamines effected phentolamine-sensitive excitatory responses of longitudinal myometrial preparations from untreated guinea-pigs. Adrenaline usually produced propranolol-sensitive inhibitory responses of longitudinal preparations from estradiol-treated animals, while noradrenaline did so only in a minority of cases. The potencies of adrenaline as an inhibitory agonist and noradrenaline as an excitatory agonist were markedly increased in preparations from estradiol-primed animals. The addition of progesterone to the steroid dosage regimen accentuated the predominance of .beta.-adrenoceptor-mediated responses of longitudinal myometrial preparations. Both catecholamines inhibited uterine contractions, and the magnitude of the inhibitory response to adrenaline was greater than that seen following estradiol priming alone. It is proposed that this selective inhibition of contractions of the longitudinal (but not the circular) myometrium by adrenaline, noradrenaline and phenylephrine, is dependent upon the induction, by estradiol, of additional cytoplasmic progesterone receptors which are available for interaction with increased levels of progesterone of either endogenous or exogenous origin.