USE OF SELECTIVE ANTAGONISTS FOR DETERMINING THE TYPES OF RECEPTORS MEDIATING THE ACTIONS OF 5-HYDROXYTRYPTAMINE AND TRYPTAMINE IN THE ISOLATED RABBIT AORTA

  • 1 January 1983
    • journal article
    • research article
    • Vol. 224  (1) , 215-221
Abstract
Competitive and noncompetitive antagonists were used to study the receptors which mediate the contraction elicited by 5-hydroxytryptamine (5-HT) and tryptamine (TRP) in the isolated rabbit aorta. The response to 5-HT was more susceptible to inhibition by competitive antagonists selective for 5-HT receptors, such as cyproheptadine, 5-methylgramine, 5-methoxygramine or 2-bromo-LSD, than was the response to TRP; the estimated apparent Kd for each antagonist was significantly lower when 5-HT rather than TRP was the agonist. If either of the 2 agonists and an antagonist are competing for the same single receptor, the Kd value should be independent of the agonist. The 5-HT response was also more sensitive to the noncompetitive antagonist, dibenamine. A noncompetitive antagonist of .alpha.-adrenergic receptors, benextramine tetrahydrochloride monohydrate (BHC), depressed the maximal TRP response 25-35% without affecting the 5-HT response. After blockade of .alpha.-adrenergic receptors with BHC, Kd values determined for each of the competitive antagonists using either 5-HT or TRP were no longer significantly different. After blockade by BHC, TRP and 5-HT, responses were equally sensitive to dibenamine. After adrenergic nerve terminals were removed by stripping off the adventitia of the aorta, the response to TRP was still partially antagonized by BHC. In this preparation TRP directly activates both .alpha.-adrenergic and 5-HT receptors and the 5-HT response is mediated by the 5-HT receptor with no involvement of .alpha.-receptors.