Effect of propranolol on rat brain synaptosomal Na(+)-K(+)-ATPase, Mg(2+)-ATPase and Ca(2+)-ATPase.
The beta blocker drug propranolol (PPL) significantly inhibited Na(+)-K(+)-ATPase, Mg(2+)-ATPase and Ca(2+)-ATPase activities in a concentration dependent manner in rat brain synaptosomes. The concentrations required for 50% inhibition (IC50) in the activity of these enzymes were 1.5-1.8 mM. The double-reciprocal plot of ATP-stimulated Na(+)-K(+)-ATPase activity in the presence of PPL showed apparent decrease in K(m) and Vmax and the inhibition was of an uncompetitive type with respect to ATP. The nature of inhibition by PPL of Na(+)-activated Na(+)-K(+)-ATPase activity was of a mixed type showing an increase in Km and decrease in Vmax. Potassium activation kinetics of Na(+)-K(+)-ATPase displayed uncompetitive type of inhibition with PPL since Km and Vmax were decreased. Magnesium activation of Mg(2+)-ATPase showed decrease in Vmax with no apparent change in Km in the presence of PPL. The drug inhibited synaptosomal Ca(2+)-ATPase in an uncompetitive manner. The observed inhibition of synaptosomal ATPases indicates possible alterations in the synaptic transmission by the beta blocker drug PPL.
Gopalaswamy
U V
UV
Radiation Biology and Biochemistry Division, Bhabha Atomic Research Centre, Bombay, India.
Satav
J G
JG
Katyare
S S
SS
Bhattacharya
R K
RK
D000319:Adrenergic beta-Antagonists / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D017301:Ca(2+) Mg(2+)-ATPase / Q000187:drug effects* / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011433:Propranolol / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects* / Q000201:enzymology
D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase