NOREPINEPHRINE ATTENUATES SEROTONIN INHIBITION OF PIAL VENOUS TONE

Serotonin (5-hydroxytryptamine, 5-HT) has been shown to inhibit the rh ythmic constrictions, accompanied by an increase in cAMP synthesis, in porcine pial veins. Since porcine pial veins contain predominant post synaptic alpha(1)-adrenoceptors which are coupled to G(1)-protein, the possibility that the inhibitory effect of 5-HT is antagonized by nore pinephrine was examined pharmacologically, using tissue bath technique s. The results indicated that norepinephrine (0.1-1 mu M) attenuated 5 -HT-induced inhibition of rhythmic constriction. This effect of norepi nephrine was mimicked by clonidine (an alpha(2)-adrenoceptor agonist), but not by methoxamine (an alpha(1)-adrenoceptor agonist). Furthermor e, the effect of norepinephrine was prevented by yohimbine (an alpha(2 )-adrenoceptor antagonist) and pertussis toxin, but was not prevented by prazosin (an alpha(1)-adrenoceptor antagonist). In parallel studies , the basal concentration of cAMP and that induced by 5-HT in the pial veins were inhibited by norepinephrine (0.3 mu M). These results are consistent with the previous findings that 5-HT-induced inhibition of rhythmic constriction in the porcine pial veins is associated with an increase in vascular cAMP synthesis and suggest that norepinephrine at tenuates 5-HT-induced inhibition of rhythmic constriction in part by n egatively coupling to adenylate cyclase via alpha(2)-adrenoceptors.