Relaxation of heart muscle by catecholamines and by dibutyryl cyclic adenosine 3',5'-monophosphate. Similarity of beta-adrenoceptors mediating contractile and relaxant effects of catecholamines in kitten pipillary muscle.
1. In isometrically contracting kitten papillary muscles, dibutyryl cyclic AMP (DBcAMP) enhanced peak tension, increased rates of contraction and relaxation, decreased tension of a phasic but not of a small tonic component of KCl-contractures, and caused aftercontractions. These effects resemble closely those of catecholamines. 2. The effects of DBcAMP on kitten papillary muscle were not influenced by (-)-bupranolol, a beta-adrenoceptor antagonist. 3. DBcAMP decreased KCl-contractures in strips of frog ventricle. 4. Phasic KCl-contractures in kitten papillary muscles were decreased by (-)- and (+)-isoprenaline. For similar effects, 100-fold higher concentrations of (+)-isoprenaline than of (-)-isoprenaline were required. 5. Increases in maximum rates of contraction and relaxation, increases in peak tension of isometric contractions and reduction of phasic KCl-contractures by catecholamines were antagonized competitively to a similar extent by (-)-bupranolol. Mean apparent equilibrium constants for the beta-adrenoceptor-(-)-bupranolol complex of 0.46-0.70 nM were estimated. These constants were quite similar irrespective of whether (-)-isoprenaline, (+)-isoprenaline or (-)-noradrenaline were used as agonists. 6. Increases in contractile strength, maximum rates of contraction and of relaxation of isometric contractions and decreases in KCl-contractures by (-)-isoprenaline were surmountably blocked by (+)-bupranolol. Mean apparent equilibrium constants for the receptor-(+)-bupranolol complex were 40-50 nM. 7. The equilibrium constants of (-)- and (+)-bupranolol for the receptors mediating positive inotropic and relaxant effects of catecholamines were not significantly different from constants for bupranolol-receptor complexes in cell-free membrane particles of kitten heart ventricle. It is suggested that the same beta-adrenoceptor triggers positive inotropic, relaxant and adenylyl cyclase-activating effects of catecholamines in kitten papillary muscle. 8. The partial agonist (-)-dichloroisoprenaline (DCI) (1 muM) reduced by 79% the phasic KCl-contractures of the kitten papillary muscles. DCI stimulates adenylyl cyclase activity of ventricle membranes to less than 1/4 of maximum stimulation by (-)-isoprenaline. If cyclic AMP produced by DCI is involved in the decrease of phasic KCl-contracture, small increase in cyclic AMP should be sufficient to induce this effect.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001001:Anura; D003994:Bucladesine / Q000494:pharmacology*; D002395:Catecholamines / Q000494:pharmacology*; D002415:Cats; D004347:Drug Interactions; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011893:Rana esculenta; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013237:Stereoisomerism
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011412:Propanolamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D003994:Bucladesine; D011189:Potassium Chloride; D007545:Isoproterenol; D009638:Norepinephrine