Differences in activity between noradrenaline and other alpha-agonists in rat vas deferens

1 The stimulating activity of methoxamine on rat vas deferens differed from that of noradrenaline since it induced a strong rhythmic activity which was not removed by the wash-out of the drug. 2 Clonidine showed a dose-response curve with a pD2 of 5.05 +/- 0.14 and an intrinsic activity value of 0.6 +/- 0.1%; B-HT 920, a specific alpha 2-agonist, elicited a very low stimulating effect (pD2 = 2.87 +/- 0.04; i.a. = 0.08 +/- 0.001). 3 In a calcium-free medium the maximum responses to synthetic alpha-adrenoceptor agonists were reduced by 98 +/- 0.8% compared with the control value. The residual response to noradrenaline, however, was significantly higher (15 +/- 0.9% of the control value). 4 At high concentration of the Ca-channel antagonists, nicardipine and verapamil, only noradrenaline showed a residual response that was resistant to the calcium channel blockers. This residual response was completely inhibited by chloroethylclonidine (10(-5) M). 5 It is proposed that the stimulating activity of the physiological adrenergic agonist, noradrenaline, is more complex when compared to that of synthetic agonists and it might result from an interaction with different alpha-adrenoceptors. 6 Both salbutamol and forskolin were able to abolish the rhythmic activity of methoxamine, suggesting a regulatory role of cAMP on membrane stability.