Very low levels of cholecystokinin octapeptide activate Na-pump in the cerebral cortex of CCK2 receptor-deficient mice.
This study provides the first evidence that CCK-8 (0.01 pM to 0.1 mM) stimulates Na,K-ATPase in the cortical membranes of wild-type and CCK(2) receptor-deficient mice. In each genotype, the maximal stimulation was about 40%. Homozygous mice revealed substantially lower EC50 (4 pM) than heterozygous (37 pM) or wild-type animals (682 pM). In homozygous CCK2 receptor-deficient mice, the expression of CCK1 receptor gene was 5-fold higher than in wild-type animals. CCK1 receptor antagonist devazepide counteracted effect of CCK-8 in all three genotypes, whereas CCK2 receptor antagonist L-365, 260 showed significant antagonism in wild-type and heterozygous mice. The cooperativity of Na,K-ATPase for Na+, but not for K+, was lost in homozygous mice. Altogether, very low concentrations of CCK-8 via CCK1 and CCK2 receptors stimulate Na,K-ATPase in the cerebral cortex. CCK2 receptor-deficiency leads to the altered functionality of Na,K-ATPase that might be compensated by CCK1 receptor mediated influence of CCK (and its agonists) on the enzyme.
Roots
Kristiina
K
Department of Biochemistry, Tartu University, Ravila 19, 50411 Tartu, Estonia.
Kairane
Czeslava
C
Salum
Tiit
T
Kõks
Sulev
S
Karelson
Ello
E
Vasar
Eero
E
Zilmer
Mihkel
M
D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D020109:Devazepide / Q000378:metabolism; D005260:Female; D006727:Hormone Antagonists / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010671:Phenylurea Compounds / Q000378:metabolism; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012844:Sincalide / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D001570:Benzodiazepinones; D006727:Hormone Antagonists; D010671:Phenylurea Compounds; D043887:Receptor, Cholecystokinin B; C058121:L 365260; D000254:Sodium-Potassium-Exchanging ATPase; D020109:Devazepide; D012844:Sincalide