Effect of gangliosides on Na,K-ATPase activity and conformation of microsomal membranes

The effect of gangliosides on activity of Na,K-ATPase and K-dependent nitrophenyl-phosphatase was studied. Gangliosides in low concentrations were shown to activate Na,K-ATPase, but to inhibit it in high concentrations. In all concentrations used the gangliosides had only an inhibitory action on K-dependent nitrophenyl-phosphatase. Inhibition of the enzyme by gangliosides was reversible and competitive relative to K⁺. Calculation of Hill's coefficient showed that gangliosides, whether their action was activating or inhibitory, behaved as allosteric effectors. To elucidate the mechanism of action of gangliosides on the enzyme their effect on microsomal membranes was studied by the fluorescent probe method. Gangliosides were found to produce marked conformational changes in microsomal membranes of the brain.Department of Pharmacology and Department of General and Clinical Chemistry, Erevan Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 12, pp. 682–684, December, 1978.     

Effect of 4-aminopyridine on cardiovascular functions in the dog

The drug 4-aminopyridine (4-AP) at a dose of 0.2 mg kg^-1 body weight intravenously is an effective antagonist of non-depolarizing neuromuscular blockade. We studied its cardiovascular effects in the canine heart using a right-heart bypass with extracorporeal circulation in seven dogs. This study demonstrates that 4-aminopyridine significantly augments arterial blood pressure, left ventricular dp/dt maximum, as well as left ventricular pressure at dp/dt mx. The highest values were obtained between two and 20 minutes after administration of 4-AP. Left ventricular end-diastolic pressure diminished slightly, but this was not statistically significant. Although the exact mechanism of action of 4-AP is not known, its positive inotropic effects may be of value in the reversal of non-depolarizing neuromuscular blockade in patients with impaired myocardial function of diverse aetiologies and it would be contraindicated in patients with arterial hypertension and/or coronary artery disease.