brl-37344 and tertatolol

Receptor autoradiography was used in guinea-pig heart to locate binding sites for the beta-adrenoceptor ligand (-)[125I]cyanopindolol (CYP) resistant to blockade by the beta-adrenoceptor antagonist (-)-propranolol (1 microM). Highly localized binding was observed to regions closely associated with the sinoatrial node, atrioventricular node and bundle of His but was not observed on myocardial, pacemaker, conducting cells or adipose tissue. Free [125I] also bound to identical sites. Binding was enhanced in the presence of ascorbic acid but was completely inhibited by (-)-isoprenaline (100 microM), serotonin (5-HT) (10 microM) and phentolamine (10 microM).

Topics: Alprenolol; Animals; Ascorbic Acid; Binding Sites; Ethanolamines; Female; Guinea Pigs; Haloperidol; Heart Conduction System; Isoproterenol; Male; Myocardium; Peroxidase; Phentolamine; Pindolol; Propanolamines; Propranolol; Protein Binding; Receptors, Adrenergic, beta; Serotonin; Thiophenes; Trachea

1. Experiments were performed to investigate the possible interaction between tertatolol and the "atypical" beta-adrenoceptor present in guinea-pig ileum. 2. In the electrically field stimulated guinea-pig ileum, both isoprenaline and BRL-37344 produce concentration-dependent inhibition of the "twitch" response. 3. Schild regression analysis of the interaction between isoprenaline and tertatolol indicated two sites of action and yielded an apparent pA2 value for tertatolol of 6.8 at the "atypical" beta-adrenoceptor. 4. BRL-37344 selectively activated the "atypical" beta-adrenoceptor and tertatolol again yielded an apparent pA2 value of 6.7 and 6.8.

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Animals; Electric Stimulation; Ethanolamines; Guinea Pigs; Ileum; In Vitro Techniques; Isoproterenol; Male; Methiothepin; Muscle Contraction; Muscle, Smooth; Propanolamines; Receptors, Adrenergic, beta; Thiophenes