Mechanisms of specific change by estradiol in sensitivity of rat uterus to serotonin.
The sensitivity (contractile response) to serotonin (5-HT) of the isolated rat uterus was increased either during estrus or by administration of estradiol to ovariectomized rats. These increases in sensitivity to 5-HT were specific, because the sensitivities to acetylcholine and oxytocin were not influenced in either case. Pargyline (10(-5) M), an inhibitor of monoamine oxidase, did not affect the contractile responses to 5-HT, acetylcholine and oxytocin of uterus from ovariectomized rats. The monoamine oxidase activities in 100,000 X g precipitates and supernatants of homogenates for uteri from ovariectomized rats were either increased or unchanged by administration of estradiol. The contractile response to 5-HT of the uterus of untreated ovariectomized rats was not affected by chlorimipramine at 10(-6) M, a concentration that inhibits 5-HT uptake. Administration of estradiol increased significantly the number of [3H]spiroperidol binding sites (5-HT receptors) from 0.56 +/- 0.04 to 1.23 +/- 0.11 pmol/mg of protein, but did not change the apparent affinity of 5-HT receptors. Administration of estradiol did not change the dissociation constant or number of binding sites for [3H]quinuclidinyl benzilate (muscarinic acetylcholine receptors) significantly. These results indicate that the specific increase in sensitivity to 5-HT on administration of estradiol is due to change in the number of 5-HT receptors, but not to change in 5-HT uptake or in metabolic degradation of 5-HT.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D004971:Estrus; D005260:Female; D008995:Monoamine Oxidase / Q000378:metabolism; D011247:Pregnancy; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects*
D011985:Receptors, Serotonin; D012701:Serotonin; D004958:Estradiol; D011813:Quinuclidinyl Benzilate; D008995:Monoamine Oxidase