Epinephrine/Lidocaine Hydrochloride

Addition of 10^-5M l-isoproterenol chloride (I chloride) [5984-95-2] to rat ventricular muscle slice preparations for 10 min increased ³²P incorporation into 100,000g particulate and 100,000g supernatant (soluble) fractions but not into homogenates or 1000 and 29,000g particulate fractions prepared from the slices.I also produced a 93% increase in ³²P incorporation and a 27% increase in inorganic phosphate in TCA-insoluble protein that was obtained from ventricular slice homogenates.An increase in the incorporation of ³²P occurred in the 100,000g particulate and supernatant fractions and the acid-insoluble protein within 2 and 1 min, resp.While the β-adrenergic blocking agent propranolol had no effect by itself on ³²P incorporation, it prevented the I-induced incorporation of ³²P into the 100,000g particulate and supernatant fractions and the acid-insoluble protein.Removal of I from the bathing medium eliminated the differences in ³²P incorporation, indicating that the effects of the catecholamine were reversible.l-Norepinephrine bitartrate [51-40-1] and l-epinephrine bitartrate [51-42-3] at 10^-5M caused phosphorylation effects similar to that of I.When the slices were bathed under anoxic conditions, I failed to enhance the incorporation of ³²P into proteins of the 100,000g particulate and supernatant fractions or acid-insoluble protein.SDS gel electrophoresis of ventricular slice homogenates revealed that I enhanced the ³²P incorporation into several myocardial proteins having mol. weights of 155, 94 (glycogen phosphorylase), 79, 68-77, and 54-59 · 10³ and decreased the incorporation into a 30 · 10³ dalton protein(s).These results are consistent with the notion that catecholamines may increase the phosphorylation of myocardial proteins in the intact myocardium which in turn may play a role in catecholamine-induced glycogenolysis and augmentation of contractility.

Isolated hepatocytes incubated with 2 mM ornithine-10 mM glutamine as substrates and challenged with either glucagon [9007-92-5], epinephrine bitartrate (I bitartrate) [51-42-3] or phenylephrine-HCl [61-76-7] exhibited stimulated rates of urea [57-13-6] production, and mitochondria isolated from these cells displayed an increased rate of energy-dependent citrulline [372-75-8] formation.There was no change in the total carbamyl phosphate synthetase (EC 2.7.2.5) [9026-23-7] I activity, nor mitochondrial content of the pos. effector N-acetyl glutamate [1188-37-0] after acute hormonal treatment.The time of onset of ureogenesis and its sensitivity to glucagon were compared with stimulation of glucose [50-99-7] production from lactate-pyruvate.No apparent differences in time of onset or sensitivity of the responses were observed indicating both pathways may be stimulated by a common mechanism.Mitochondria prepared from cells treated with catecholamines exhibited increased rates of State 3 respiration and increased uncoupler-dependent ATPase [9000-83-3] activity, in addition to the increased rates of citrulline formation.There was also an elevated intramitochondrial content of ATP [56-65-5] and an increased ATP/ADP [58-64-0] ratio.The catecholamine-induced stimulation of ureogenesis was mediated by an α-adrenergic cyclic AMP [60-92-4] independent mechanism.The addition of the α-adrenergic antagonist, dihydroergotamine, blocked both the I-induced stimulation of ureogenesis and also the stimulated functions in the isolated mitochondria.dl-Propranolol, a β-antagonist, inhibited the rise in cyclic AMP due to I, but had no effect on any of the other reactions measured.The effects of catecholamines on citrulline formation and urea production are correlated with the increased capacity of the mitochondria to generate ATP.Apparently, both glucagon and catecholamines, acting via independent mechanisms, stimulate electron transport and the activity of the ATP-forming enzyme complex.The consequent elevated intramitochondrial ATP levels and ATP/ADP ratio enhance the rate of citrulline formation and hence ureogenesis.