Electrophysiological and contractile responses of canine atrial tissue to adrenocorticotropin.
The direct extra-adrenal actions of adrenocorticotropin 1-39 (ACTH) on electrical (E) and mechanical (M) characteristics of canine atrial tissues (AT) were investigated in in vitro experiments. One hundred twenty-five mU/ml of ACTH 1-39 significantly augmented the catecholamine induced positive inotropism as seen by shortening the time to peak tension (10.6%, p = 0.01) and increasing peak isometric tension (3.5 times, p = 0.001). Effects on the M responses were inhibited by propranolol (10(-6) M) (P). ACTH did not significantly modify action potential E or M parameters during cholinergic receptor antagonism or alpha-adrenergic receptor antagonism. Existence of a specific ACTH receptor was demonstrated using 125I radioiodinated ACTH 1-24. Significant binding of 125I-ACTH to AT was observed. Intracellular C-AMP levels were also measured in AT using radioimmunoassay. Tissues were exposed to 125mU/ml ACTH 1-39 plus combinations of norepinephrine (10(-6) M) (NE) and P. ACTH alone did not elevate intracellular C-AMP levels. NE increased C-AMP levels were not further increased by ACTH. Exposure to antagonist returned elevated C-AMP levels to control values. In conclusion (1) ACTH augments the NE induced M positive inotropism of the beta adrenergic receptor system. (2) ACTH specifically binds to AT and (3) ACTH does not utilize the C-AMP second messenger system.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D016275:Atrial Function; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D018043:Receptors, Corticotropin
D011956:Receptors, Cell Surface; D018043:Receptors, Corticotropin; D000324:Adrenocorticotropic Hormone; D011433:Propranolol; D000242:Cyclic AMP; D009638:Norepinephrine