Alterations of in-vitro 5-HT receptor pharmacology as a function of multiple treatment with 5-hydroxytryptamine or 8-hydroxy-2-(di-N-propylamino) tetralin in rat isolated aorta, uterus and fundus, and guinea-pig isolated trachea.

Abstract

The effects of single and multiple (5, 10, or 15 days) administration of the 5-HT1A agonist 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT) (3 mg kg-1, i.p.) or 5-HT (3 mg kg-1, i.p.) in-vivo on the response of selected isolated smooth muscles to 5-HT in-vitro were investigated. Single dosing with 8-OH-DPAT did not alter the responses of the isolated tissues (rat aorta, uterus or fundus, or guinea-pig trachea) to 5-HT, while multiple dosing with 8-OH-DPAT produced rightward shifts and a suppression of the maximum response of all these tissues to 5-HT, with the exception of the rat stomach fundus. Multiple administration of 5-HT had no effect on the in-vitro response of the tissues to 5-HT. These data indicate that multiple administration of 8-OH-DPAT desensitizes or down-regulates the peripheral 5-HT2 receptors found on the rat aorta and uterus, and guinea-pig trachea.