Histamine alters prostaglandin output from diestrous rat uteri. Involvement of H2-receptors and 9-keto-reductase.
The effects of exogenous histamine (H) on prostaglandin (PG) generation and release in uteri isolated from diestrous rats and the influences of H2-receptors blockers (cimetidine and metiamide) on the output of uterine PGs, were explored. Moreover, the action of H on the uterine 9-keto-reductase, was also studied. Histamine (10(-4) M) failed to alter the basal output of PGE1 but reduced significantly the generation and release of PGE2 and augmented the output of PGF2 alpha. On the other hand, cimetidine (10(-5) M) enhanced the basal release of PGE2 but had no action on the outputs of PGs E1 or F2 alpha. The enhancing effect of H on the production and release of PGF2 alpha was abolished in the presence of cimetidine. Also, the antagonist reversed the influence of H on the output of PGE2. Metiamide, another H2-receptor antagonist, did not alter the basal control generation and release of uterine PGs, but antagonized the augmenting influence of H on PGF2 alpha uterine output, as much as cimetidine did, and prevented the depressive action of H on the release of PGE2 from uteri. Histamine (10(-4) M) significantly stimulated uterine formation of cyclic-adenosine monophosphate, an action which was antagonized by the presence of cimetidine (10(-5) M), a blocker of H2 receptors. Also, histamine (10(-5) M) and dibutyrylcyclic-adenosine monophosphate (DB-cAMP) at 10(-3) M, enhanced significantly the formation 3H-PGF2 alpha from 3H-PGE2. Results presented herein demonstrate that H is able to diminish the generation of PGE2 in uteri from rats at diestrus augmenting the synthesis of PGF2 alpha, apparently via the activation of H2-receptors, enhancing adenylate-cyclase. These effects appear to increase uterine 9-keto-reductase activity which transforms PGE2 into PGF2 alpha. Relationships between the foregoing results and those evoked by estradiol, are also discussed.
Viggiano
M
M
Centro de Estudios Farmacológicos y de Principios Naturales, Buenos Aires, Argentina.
Franchi
A M
AM
Faletti
A
A
Gimeno
M A
MA
Gimeno
A L
AL
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004031:Diestrus / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism; D004971:Estrus / Q000378:metabolism*; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism*; D066298:In Vitro Techniques; D008785:Metiamide / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D011970:Receptors, Histamine H2 / Q000187:drug effects*; D014599:Uterus / Q000378:metabolism*
D011453:Prostaglandins; D011970:Receptors, Histamine H2; D008785:Metiamide; D004958:Estradiol; D002927:Cimetidine; D006632:Histamine; D000242:Cyclic AMP; D006911:Hydroxyprostaglandin Dehydrogenases; C035858:prostaglandin-E2 9-reductase