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 invol ved 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 ao rta 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-Meth ylurapidil (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-adrenocep tor agonists in a similar range of concentrations in which they elicit ed contraction. Moreover, 8-OH-DPAT and buspirone protected the alpha- adrenoceptors from the irreversible blockade provoked by phenoxybenzam ine (10(-7) M), as judged by the norepinephrine contraction and stimul ated phosphatidylinositol labeling. According to these results the con tractile 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-adrenocep tors, whereas both alpha1A- and alpha1B-adrenoceptors may mediate the effect of buspirone in rabbit aorta.