α₁- and α₂-adrenoceptors of the circular myometrium from the dioestrous guinea-pig

1. In order to investigate the nature of the α‐adrenoceptors mediating contraction of circular myomctrium from dioestrous guinea‐pigs, the effects of several adrenoceptor antagonists upon log concentration curves to noradrenaline and phenylephrine have been examined. 2. In the presence of ICI 118,551 and nisoxetine both phenylephrine and noradrenaline produced concentration‐dependent contractures of circular myometrium from virgin dioestrous guinea‐pigs. Noradrenaline was the more potent and produced larger maximal contractions. Indomethacin (1 μmol/l) decreased the maximum effects of phenylephrine but not those of noradrenaline. Xylazine produced indomelhacin‐sensitive contractions which were not dose‐related and which never exceeded 40% of those evoked by noradrenaline. Responses to xylazine and to noradrenaline, but not those to phenylephrine, were reduced in a low calcium solution. 3. Prazosin produced competitive antagonism of the effects of phenylephrine upon preparations of circular myometrium from virgin and parous dioestrous animals; pA₂ values were both 8.1. Phentolamine also competitively antagonized the effects of phenylephrine (virgin animals, pA₂= 7.7). 4. Both prazosin and phentolamine antagonized the effects of noradrenaline upon preparations from virgin dioestrous animals, however, Schild plot analysis did not indicate a simple bimolecular interaction between agonist and receptors. In the presence of prazosin the α₂‐adrenoceptor antagonist idazoxan produced dose‐dependent parallel shifts in the positions of the log concentration‐response curves to noradrenaline; the pA₂ was 7.7. In the presence of idazoxan or of indomethacin prazosin competitively antagonized the effects of noradrenaline; the pA₂ values were 8.5 and 8.2 respectively. 5. The present findings indicate that the effects of noradrenaline upon the contractility of the circular myometrium of dioestrous guinea‐pigs may result from activation of both α₁‐ and α₂‐adrenoceptors.