PHARMACOLOGICAL EVIDENCE FOR INTERACTIONS BETWEEN 5-HT(1A)RECEPTOR AGONISTS AND SUBTYPES OF ALPHA(1)-ADRENOCEPTORS ON RABBIT AORTA

This study was designed to determine if alpha1-adrenoceptors are involved in the vascular responses to 5-HT1A receptor agonists. Buspirone (3.1 X 10(-7)-3.1 X 10(-5) M) and 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT; 3.1 x 10(-6)-10(-4) M) elicited contractions of rabbit aorta rings which were blocked by prazosin (10(-9)-5.6 x 10(-9) M), but which were unaffected by reserpine pretreatment (1 mg/kg i.p.). 5-Methylurapidil (10(-7) and 10(-6) M) blocked contractions elicited by 8-OH-DPAT and by buspirone, whereas chloroethylclonidine (10(-5) and 10(-4) M) inhibited only the effect of buspirone. In addition, these 5-HT1A receptor agonists relaxed arteries precontracted with alpha-adrenoceptor agonists in a similar range of concentrations in which they elicited contraction. Moreover, 8-OH-DPAT and buspirone protected the alpha-adrenoceptors from the irreversible blockade provoked by phenoxybenzamine (10(-7) M), as judged by the norepinephrine contraction and stimulated phosphatidylinositol labeling. According to these results the contractile and relaxant effects elicited by 5-HT1A receptor agonists are a consequence of a direct interaction with alpha1-adrenoceptors. The contraction elicited by 8-OH-DPAT may be mediated by alpha1A-adrenoceptors, whereas both alpha1A- and alpha1B-adrenoceptors may mediate the effect of buspirone in rabbit aorta.