Mediation of 5‐hydroxytryptamine‐induced tachycardia in the pig by the putative 5‐HT4 receptor

Abstract

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.