Viggiano M, Franchi A M, Faletti A, Gimeno M A, Gimeno A L
Centro de Estudios Farmacológicos y de Principios Naturales, Buenos Aires, Argentina.
Prostaglandins. 1988 Sep;36(3):317-28. doi: 10.1016/0090-6980(88)90073-1.
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.
研究了外源性组胺（H）对从处于动情间期的大鼠分离出的子宫中前列腺素（PG）生成和释放的影响，以及H2受体阻滞剂（西咪替丁和甲硫咪特）对子宫PGs分泌的影响。此外，还研究了H对子宫9-酮还原酶的作用。组胺（10(-4)M）未能改变PGE1的基础分泌量，但显著降低了PGE2的生成和释放，并增加了PGF2α的分泌量。另一方面，西咪替丁（10(-5)M）增强了PGE2的基础释放，但对PGs E1或F2α的分泌量没有影响。在存在西咪替丁的情况下，H对PGF2α生成和释放的增强作用被消除。此外，该拮抗剂逆转了H对PGE2分泌量的影响。另一种H2受体拮抗剂甲硫咪特，没有改变子宫PGs的基础控制生成和释放，但与西咪替丁一样，拮抗了H对子宫PGF2α分泌量的增强作用，并阻止了H对子宫中PGE2释放的抑制作用。组胺（10(-4)M）显著刺激子宫中环磷酸腺苷的形成，这一作用被H2受体阻滞剂西咪替丁（10(-5)M）的存在所拮抗。此外，组胺（10(-5)M）和10(-3)M的二丁酰环磷酸腺苷（DB-cAMP）显著增强了由3H-PGE2生成3H-PGF2α的过程。本文给出的结果表明，H能够减少处于动情间期大鼠子宫中PGE2的生成，增加PGF2α的合成，显然是通过激活H2受体、增强腺苷酸环化酶来实现的。这些作用似乎增加了子宫9-酮还原酶的活性，该酶将PGE2转化为PGF2α。还讨论了上述结果与雌二醇所引发结果之间的关系。
