title: Resistance of adrenergic neurotransmission in the toad heart to adrenoceptor blockade.
abstract: Stimulation of sympathetic nerves to the toad heart produced increases in both the rate and force of cardiac beat. Although these responses were abolished by treatment with bretylium (10-6 mol.1-1) or 6-hydroxydopamine (100 mg.kg-1), and surgical sympathetic denervation, they were not abolished by treatment with propranolol (10-6 mol-1-1) and phentolamine (3 X 10-6 mol.1-1), either alone or in combination. The responses remaining after adrenoceptor blockade could not be ascribed to the effects of neurally released dopamine, ATP, adenosine, histamine or a variety of neuropeptides, although the participation of an as yet unidentified co-transmitter cannot be ruled out. Quantitative analysis of the interactions between propranolol and adrenaline on cardiac adrenoceptors, after blockade of alpha-receptors and amine uptake mechanisms, revealed that these interactions do not comply with the conditions for simple competitivity. Therefore, in addition to its action on beta-receptors, adrenaline seems to be producing excitation of the toad heart by acting on adrenoceptors which cannot be classified as either alpha- or beta-receptors. These results, together with the existence of close neuromuscular gaps (less than 50 nm) in the toad heart, are consistent with the hypothesis that sympathetic excitation of the toad heart is mediated by both "extra-junctional" beta-adrenoceptors, and "junctional" adrenoceptors which are neither alpha- nor beta-receptors.
mesh_terms: D000818:Animals; D001949:Bretylium Compounds / Q000494:pharmacology; D002024:Bufo marinus / Q000502:physiology*; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000294:innervation / Q000502:physiology*; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology*; D012601:Scopolamine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology*; D009435:Synaptic Transmission
chemical_list: D001949:Bretylium Compounds; D011941:Receptors, Adrenergic; D011433:Propranolol; D012601:Scopolamine; D010646:Phentolamine