Functional Interactions between 5-Hydroxytryptamine Receptors and the Serotonin Transporter in Pulmonary Arteries

Pulmonary arterial 5-hydroxytryptamine (serotonin) (5-HT) transporter (SERT)-, 5-HT receptor expression, and 5-HT-induced vasoconstriction can be increased in pulmonary hypertension. These variables were studied in normoxic and hypoxic Fawn-Hooded (FH) and Sprague-Dawley (SD) rats. Furthermore, we compared the functional effects of SERT inhibitors and 5-HT receptor antagonists against 5-HT-induced vasoconstriction of pulmonary arteries. SERT and 5-HT1B expression was greater in FH rat lungs than in SD rats, as was 5-HT-mediated vasoconstriction. The 5-HT2A receptor antagonist ketanserin and the 5-HT1B receptor antago-nist SB224289 (1-methyl-5-[[2-methyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydro-spiro-[furo] 2, 3-f]indole-3,4-piperidine]) inhibited responses to 5-HT i