Is the 5-hydroxytryptamine 7 Receptor Constitutively Active in the Vasculature? A Study in Veins/Vein

Abstract: The 5-hydroxytryptamine 7 (5-HT7) receptor is reported to have considerable constitutive activity when transfected into cells. Constitutive activity—receptor activity in the absence of known agonist—is important for understanding the contributions of a receptor to (patho)physiology. We test the hypothesis that the 5-HT7 receptor possesses constitutive activity in a physiological situation. Isolated veins from male and female Sprague Dawley rats were used as models for measuring isometric force; the abdominal vena cava possesses a functional 5-HT7 receptor that mediates relaxation, whereas the small mesenteric vein does not. Compounds reported to act as inverse agonists were investigated for their ability to cause contraction (moving a constitutively active relaxant receptor to an inactive state, removing relaxation). Compared with a vehicle control, clozapine, risperidone, ketanserin, and SB269970 caused no contraction in the isolated male abdominal vena cava. By contrast, methiothepin caused a concentration-dependent contraction of the male but not female abdominal vena cava, although with low potency (−log EC50 [M] = 5.50 ± 0.45) and efficacy (∼12% of contraction to endothelin-1). Methiothepin-induced contraction was not reduced by the 5-HT7 receptor antagonist (SB269970, 1 μM, not active in the vena cava). These same compounds showed little to no effect in the isolated mesenteric vein. We conclude that the 5-HT7 receptor in the isolated veins of the...
Source: Journal of Cardiovascular Pharmacology - Category: Cardiology Tags: Original Article Source Type: research