Epinephrine/Lidocaine Hydrochloride

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.

A purified neurotoxin from the venom of black widow spider Latrodectus mactans tredecimguttatus, when tested on synaptosomes by means of a perfusion technique, stimulates the release of previously accumulated radioactive transmitters.Black widow spider toxin has also been shown to be a potent inhibitor of the uptake systems for γ‐aminobutyrate and N‐epinephrine. The release from synaptosomes of radioactive N‐epinephrine and γ‐aminobutyrate was rapidly increased by the presence of a low concentration of toxin (∼ 1 nM). The toxin does not appear to cause either non‐specific membrane damage or the release of a non‐transmitter substance like γ‐amino[14C]isobutyric acid.The venom‐induced release of γ‐aminobutyrate was shown not to be dependent on extracellular calcium concentration provided that sodium ions are present. By contrast, that of N‐epinephrine appeared to be Ca‐dependent. The release of γ‐aminobutyrate induced by the toxin is not modified by the presence in the perfusing fluid of tetrodotoxin, dithioerythritol and strontium ions, or by pretreatment of synaptosomes with diaminobutyrate. The mechanism of toxin‐induced release is different from that of a depolarization‐induced release.By correlating previous electrophysiological observations with the results obtained in this biochemical study it may be suggested that the toxin can be used in studies aimed at the identification of components specific to the presynaptic terminal membrane involved in neurotransmitter release.