Role of 5-HT2 receptors in serotonin-induced contraction in the human mammary artery.

ABSTRACT

We studied the effects of serotonin (5-HT) on isolated human mammary arteries obtained from patients undergoing coronary by-pass grafting. 5-HT induced a concentration-dependent contractile response in the mammary artery, with an EC50 value of 0.34 microM. The 5-HT2 antagonist, ketanserin, reversed the contractions evoked by 5-HT in a competitive manner at a low concentration (10(-8) M), whereas non-competitive antagonism was apparent at higher concentrations (5 X 10(-8)-5 X 10(-7) M). To investigate whether the alpha 1-blocking component of ketanserin plays a role in the response observed in this vessel, we evaluated the effect of ketanserin on contractions induced by (-)-norepinephrine. Ketanserin, in concentrations up to 10(-7) M, did not influence the norepinephrine-induced contractions. Moreover, a threshold concentration of 5-HT (10(-7) M) amplified the contractile effect induced by norepinephrine (5 X 10(-8) M), and this response was inhibited by ketanserin (10(-7) M). The selective 5-HT3 antagonist, GR 38032F, did not affect the 5-HT-induced contractions. These findings indicate that the human mammary artery is a vascular tissue sensitive to 5-HT. The 5-HT2 receptor subtype appears to mediate the response.