Abstract

This study was designed to determine the subtypes of 5-HT receptors present in bovine large coronary arteries and to characterize the response mediated by each subtype of receptor. Concentration-response relationships for 8-hydroxy-2-(di-n-propylamino)-tetralin (5-HT1A agonist) (0.3-100 microM), CGS-12066B maleate (5-HT1B agonist) (0.01-30 microM), alpha-methylserotonin maleate (5-HT2 agonist) (0.01-30 microM), 1-(m-chlorophenyl)-biguanide (5-HT3 agonist) (0.1-100 microM) and serotonin (0.1-300 microM) were studied in vitro using 2-mm segments of bovine proximal left anterior descending coronary artery. Each segmental ring was mounted in a 70-ml tissue bath for the measurement of isometric tension. 8-Hydroxy-2-(di-n-propylamino)-tetralin (10-100 microM), alpha-methylserotonin maleate (0.01-30 microM) and serotonin (0.1-300 microM) induced endothelium-independent contraction, whereas CGS-12066B maleate and 1-(m-chlorophenyl)-biguanide had no effect in this species. Contractions induced by 8-hydroxy-2-(di-n-propylamino)-tetralin or alpha-methylserotonin maleate were attenuated by pretreatment with S(-)propranolol (2.6 microM), a relatively selective 5-HT1A and 5-HT1B receptor antagonist, and ketanserin (0.3 microM), a selective 5-HT2 receptor antagonist, respectively. Pretreatment with S(-)propranolol or ketanserin also attenuated serotonin-induced contraction, demonstrating that serotonin mediates contraction through both 5-HT1A and 5-HT2 receptors in bovine large coronary arteries.