Actions of forskolin and isoprenaline on the separated myometrial layers of the guinea-pig uterus: influence of ovarian steroids and pregnancy

Hall, Solveiga; Pennefather, Jocelyn N.

doi:10.1016/0014-2999(90)90664-r

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“…In previous studies from this laboratory we have demonstrated that there are differences in the responsiveness of the circular and longitudinal myometrial layers of the guinea- pig uterus to sympathomimetic amines. These differences are particularly evident in pregnant and post-partum animals, and in animals treated with ovarian steroids (Hartley et al, 1983a;Adam et al, 1984Adam et al, , 1985Hall & Pennefather, 1990). We have now demonstrated an underlying heterogeneity in the a,-adrenoceptor populations present in the two uterine layers of the dioestrous guinea-pig.…”

Section: Discussionmentioning

confidence: 64%

“…The numbers of P,-adrenoceptors present in the circular and longitudinal layers of the dioestrous guinea-pig uterus are similar (Handberg et al, 1988); however, these receptors are more efficiently coupled to effectors in the longitudinal than in the circular myometrial layer (Hartley et al, 1983a, b;Hall & Pennefather, 1990). We therefore included the P,-adrenoceptor antagonist ICI 118, 551 (Bilski et al, 1983) in the bathing medium in all our experiments.…”

Section: Discussionmentioning

confidence: 99%

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Heterogeneity of α₁‐adrenoceptors in the guinea‐pig uterus

Haynes

Pennefather

1993

Journal of Autonomic Pharmacology

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1 The aim of this study was to identify the a,-adrenoceptor subtypes present on the circular and longitudinal myometrial layers of the dioestrous guinea-pig uterus.2 Homogenate binding studies using [3H]WB-4 10 1 identified one saturable binding site in preparations of circular myometrium. Pre-incubation of homogenates with chloroethylclonidine (50 ,UM) reduced binding by N 82%. Noradrenaline competed for two [3H]WB-4 10 1 binding sites except after chloroethylclonidine pre-incubation, when it competed for one site only.3 Only one saturable [3H]WB-4101 binding site was present, in low density, in homogenates of the longitudinal myometrium; binding to this site was unaffected by chloroethylclonidine.4 In the combined presence of nisoxetine and ICI 118,551 1, phenylephrine and noradrenaline caused sustained contractures of the circular, but not of the longitudinal myometrium. Chloroethylclonidine (50 ,UM) caused a greater inhibition of responses to phenylephrine than of those to noradrenaline.5 In preparations of circular myometrium, WB-4 10 1 competitively antagonized contractile responses to phenylephrine in both the absence and presence of idazoxan (pA2 values= 8.22, 8.00 respectively); but competitively antagonized responses to noradrenaline only in the presence of idazoxan (pA2= 8.00). Noradrenaline and phenylephrine increased the accumulation of [3H]-inositolphosphates in the circular myometrium, noradrenaline was more potent than phenylephrine (neg log EC,,,s 5.05 and 3.46 respectively). The pre-incubation of tissues in chloroethylclonidine (50 ,UM) reduced the accumulation of [3H]-inositol phosphates induced by noradrenaline, and abolished that induced by phenylephrine.7 These results indicate that the predominant a,-adrenoceptor present on the circular myometrium of the dioestrous guinea-pig is of the a,B-subtype. The longitudinal myometrium lacks this adrenoceptor.Correspondence: John M. Haynes.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%