MEDIATION OF 5-HYDROXYTRYPTAMINE-INDUCED TACHYCARDIA IN THE PIG BY THE PUTATIVE 5-HT4-RECEPTOR

Intravenous bolus injections of 5-hydroxytryptamine (5-HT; 3, 10 and 30 μg kg-1), 5-methoxytryptamine (5-MeO-T; 3, 10 and 30 μg kg-1), renzapride (BRL 24924; 3, 10, 30 and 100 μg kg-1) and isoprenaline (0.03, 0.1 and 0.3 μg kg-1) to anaesthetized pigs increased heart rate by, respectively, 22 ± 3, 44 ± 3 and 65 ± 4 beats min-1 (5-HT; n = 17); 12 ± 1, 26 ± 2 and 44 ± 4 beats min-1 (5-MeO-T; n = 15), 5 ± 2, 11 ± 2, 18 ± 4 and 37 ± 5 beats min-1 (renzapride; n = 8) and 17 ± 2, 46 ± 3 and 75 ± 3 beats min-1 (isoprenaline; n = 13). The responses to 5-HT, 5-MeO-T and renzapride were antagonized by ICS 205-930 (1 and 3 mg kg-1, i.v.), which did not modify the increases in heart rate by isoprenaline. Renzapride showed tachyphylaxis and attenuated the responses to 5-HT. These findings indicate that 5-HT elicits tachycardia in the pig by acting on a novel receptor, either similar or identical to the 5-HT4 receptor identified in mouse brain colliculi.