A 5-HT4-like receptor in human left atrium

Summary 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 I pmol/l (to block -adrenoceptors) and cocaine 6 gmol/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 mol/l) and 25% of that caused by 6.75 mmol/l CaCl₂. The, effects of 5-HT were competitively antagonised by 3-tropanyl-1H-indole-3-carboxylate (ICS 205–930) with a pK_B 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.Send offprint requests to A. J. Kaumann at the above address