Role of alpha-adrenoceptors in the effects of buspirone and 5-carboxamidotryptamine in rabbit isolated thoracic aorta.
1. The role of alpha-adrenoceptors in the vascular effects of buspirone (BUS) and 5-carboxamidotryptamine (5-CT) was investigated in rabbit thoracic aorta. 2. Buspirone produced a concentration-dependent contraction. The non-selective 5-HT1 and 5-HT2-receptor antagonist methysergide and the 5-HT2 receptor antagonist ketanserin did not alter the contractile effect of buspirone. However, the competitive antagonist of alpha 1-adrenoceptors, prazosin, shifted the concentration-response curve of buspirone to the right without changing the maximal response. 3. Benextramine tetrahydrochloride monohydrate (BHC), a noncompetitive antagonist of alpha 1-adrenoceptors, inhibited the contraction induced by buspirone in a noncompetitive manner. After pretreatment with two different concentrations of BHC, the estimated apparent dissociation constants of buspirone were found to be identical. 4. In addition, buspirone antagonized the concentration-response curve of phenylephrine again showing a similar dissociation constant, suggesting a partial agonistic action of buspirone at the level of alpha 1-adrenoceptors. 5. The concentration-response curve of 5-HT showed two components in the thoracic aorta obtained from reserpine treated and untreated animals as verified by different pD2 values. The second component was observed with relatively higher concentrations of 5-CT and could be blocked by prazosin or BHC. Neither of these compounds altered the first component. After Pretreatment with BHC, the first component of 5-CT was competitively antagonized by methysergide and ketanserin, having pA2 values of 8.81 and 9.1 respectively. 6. These results suggest that the contraction induced by buspirone is mainly mediated by alpha 1-adrenoceptors, while the higher concentrations of 5-CT caused contraction via alpha 1-adrenoceptor stimulation in addition to its 5-HT2 agonistic effect.
Department of Pharmacology, Medical School of Ankara University, Turkey.
H
H
Gürdal
H O
HO
Onaran
F C
FC
Tulunay
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002065:Buspirone / Q000494:pharmacology*; D003538:Cystamine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007650:Ketanserin / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D010656:Phenylephrine; D012701:Serotonin; C029998:benextramine; C047087:5-carboxamidotryptamine; D007650:Ketanserin; D003538:Cystamine; D002065:Buspirone; D011224:Prazosin; D008784:Methysergide