HETEROGENEITY OF ALPHA-1-ADRENOCEPTORS IN THE GUINEA-PIG UTERUS

1 The aim of this study was to identify the alpha1-adrenoceptor subtypes present on the circular and longitudinal myometrial layers of the dioestrous guinea-pig uterus. 2 Homogenate binding studies using [H-3]WB-4101 identified one saturable binding site in preparations of circular myometrium. Pre-incubation of homogenates with chloroethylclonidine (50 mum) reduced binding by almost-equal-to 82%. Noradrenaline competed for two [H-3]WB-4101 binding sites except after chloroethylclonidine pre-incubation, when it competed for one site only. 3 Only one saturable [H-3]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, phenylephrine and noradrenaline caused sustained contractures of the circular, but not of the longitudinal myometrium. Chloroethylclonidine (50 muM) caused a greater inhibition of responses to phenylephrine than of those to noradrenaline. 5 In preparations of circular myometrium, WB-4101 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). 6 Noradrenaline and phenylephrine increased the accumulation of [H-3]-inositol phosphates in the circular myometrium, noradrenaline was more potent than phenylephrine (neg log EC50s 5.05 and 3.46 respectively). The pre-incubation of tissues in chloroethylclonidine (50 mum) reduced the accumulation of [H-3]-inositol phosphates induced by noradrenaline, and abolished that induced by phenylephrine. 7 These results indicate that the predominant alpha1-adrenoceptor present on the circular myometrium of the dioestrous guinea-pig is of the alpha1B-subtype. The longitudinal myometrium lacks this adrenoceptor.