A 5-HT4-like receptor in human left atrium

Abstract

The effects of 5-hydroxytryptamine (5-HT) on left atrial preparations obtained from 5 patients with terminal heart failure who were undergoing heart transplant surgery were investigated. The preparations were paced under isometric conditions. In the presence of (-)-pindolol 1 mumol/l (to block beta-adrenoceptors) and cocaine 6 mumol/l (to block tissue uptake of 5-HT) 5-HT increased contractile force with a pEC50 of 7.0. The maximum effect of 5-HT amounted to 24.5% of that caused by a maximally effective concentration of (-)-isoprenaline (200 mumol/l) and 25% of that caused by 6.75 mmol/l CaCl2. The effects of 5-HT were competitively antagonised by 3 alpha-tropanyl-1H-indole-3-carboxylate (ICS 205-930) with a pKB of 6.8. The effects of 5-HT on cyclic AMP levels and cyclic AMP-dependent protein kinase activity were also studied using left atrial tissues from one of the patients; 5-HT increased the cyclic AMP content and stimulated the kinase. The results are consistent with the existence of a human left atrial 5-HT receptor which is similar to the recently identified human right atrial 5-HT receptor that resembles the 5-HT4 receptor. The left atrial 5-HT4-like receptor is functional in tissues obtained from patients with terminal heart failure.