1. The present study was to ascertain whether drugs cause differential antagonism of the initial fast and secondary slow contractile responses to phenylephrine, 5-HT and methacholine of the rat portal vein. 2. Cocaine (5 x 10(-6) M) had no effect on the responses to methacholine. Cocaine potentiated the initial fast but not the secondary slow responses to phenylephrine suggesting that neuronal uptake limits the initial fast but not the secondary slow response to phenylephrine. Cocaine reduced the maximal responses to 5-HT suggesting that the responses to high concentrations of 5-HT are due, in part, to the release of noradrenaline. 3. In the presence of cocaine, idazoxan had no effect on responses to phenylephrine or 5-HT and prazosin had no effect on responses to 5-HT. Prazosin (3 x 10(-9)-10(-8) M) inhibited the responses to phenylephrine causing similar parallel rightward shifts of the concentration-response curves to the initial fast and secondary slow responses. 4. In the presence of cocaine, mianserin (10(-9)-10(-8) M), cyproheptadine, (10(-10)-10(-9) M), methysergide (10(-8) M), ketanserin (10(-10)-10(-9) M) and Ly 53857 (at 10(-9)-10(-8) M) had similar inhibitory effects on the initial fast and secondary slow responses to 5-HT, namely a parallel rightward displacement of the concentration-response curves. 5. Atropine (less than or equal to 10(-7) M) and pirenzepine less than or equal to 10(-6) M) had no effect on the responses to phenylephrine and 5-HT, but caused similar parallel rightward shifts of the concentration-response curves to both responses to methacholine. 6. The results of this study provide no evidence for differential antagonism of the initial fast and secondary slow responses of the rat portal vein to phenylephrine, 5-HT or methacholine.
Adrenergic alpha-Antagonists Animals