Role of alpha-adrenoceptors in the effects of buspirone and 5-carboxamidotryptamine in rabbit isolated thoracic aorta

Gen Pharmacol. 1992 Jan;23(1):43-7. doi: 10.1016/0306-3623(92)90045-l.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Aorta, Thoracic / drug effects
  • Buspirone / pharmacology*
  • Cystamine / analogs & derivatives
  • Cystamine / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Ketanserin / pharmacology
  • Methysergide / pharmacology
  • Phenylephrine / pharmacology
  • Prazosin / pharmacology
  • Rabbits
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, alpha / physiology*
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology
  • Serotonin / analogs & derivatives*
  • Serotonin / pharmacology
  • Vasoconstriction / drug effects*

Substances

  • Adrenergic alpha-Antagonists
  • Receptors, Adrenergic, alpha
  • Receptors, Serotonin
  • Phenylephrine
  • Serotonin
  • benextramine
  • 5-carboxamidotryptamine
  • Ketanserin
  • Cystamine
  • Buspirone
  • Prazosin
  • Methysergide