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 100μgkg−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.