Buspirone, a 5-HT(1A) receptor agonist, dilates the perfused rat uterine vascular bed through alpha(1)-adrenoceptor blockade.
In the perfused rat uterine vascular bed, 5-hydroxytryptamine (5-HT) produced dose-dependent vasoconstrictor responses. Buspirone, a selective 5-HT(1A) receptor agonist, was not effective at low doses but produced a response at high doses. When perfusion pressure was raised with phenylephrine, responses to 5-HT were enhanced while buspirone produced dose-dependent vasodilator responses. Buspirone did not produce vasodilation when perfusion pressure was raised with vasopressin or U46619. Buspirone-induced vasodilator responses were not affected by selective 5-HT(1A) receptor antagonists, 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]-decane-7,9-dione (BMY 7378) and N-tert-butyl-3-(4-[2-methoxyphenyl]piperazin-1-yl)-2-phenylpropanamide (WAY 100478), indicating that specific 5-HT(1A) receptors might not be involved in buspirone-induced vasodilation. Buspirone (3 x 10 (-5) M) and prazosin (3 x 10(-9) M) antagonized noradrenaline-induced constriction with dose ratios of 19.1+/-2.9 and 11.7+/-2.1, respectively. The dose ratio of these antagonists in combination was 46.6+/-8.1. Since the combination ratio is closer to the sum of their individual dose ratios less 2 (i.e. DR(p)+DR(b)-2) than it is to the product of their individual dose ratios, our data suggest an interaction of buspirone with alpha(1)-adrenoceptors. Buspirone also protected adrenoceptors against inactivation by phenoxybenzamine confirming that buspirone interacted with alpha(1)-adrenoceptors. We concluded that buspirone-induced vasodilation of the perfused rat uterine vascular bed is mediated through blockade of alpha(1)-adrenoceptors rather than through 5-HT(1A) receptors.
Adeagbo
A S
AS
Department of Physiology and Biophysics, University of Louisville, Louisville, KY, USA.
Kadavil
E A
EA
Yousif
M
M
Oriowo
M A
MA
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D002065:Buspirone / Q000819:agonists*; D005260:Female; D023421:Models, Animal; D009215:Myometrium / Q000098:blood supply* / Q000187:drug effects*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D002065:Buspirone