Inhibition of brain protein kinase C attenuates immobilization stress-induced plasma corticosterone levels in mice.
To evaluate the involvement of brain protein kinase C (PKC) in the stress-induced activation of hypothalamic-pituitary-adrenal (HPA) axis, we examined the effects of PKC inhibitors administered intracerebroventricularly (i.c.v.) on the immobilization stress-induced plasma corticosterone levels in mice. Calphostin C (a pan-specific PKC inhibitor) injected i.c.v. decreased the immobilization stress-induced plasma corticosterone level: maximal inhibition of 35% was attained at a dose of 100 pmol. Gö 6976 (an alpha and beta1 PKC isotype-selective inhibitor) was less effective than Calphostin C: maximal inhibition of 17% was attained at a dose of 30 pmol. Phorbol 12-myristate 13-acetate (a general PKC activator) injected i.c.v. at doses of 16 and 48 pmol increased the plasma corticosterone levels in a dose-dependent manner. The present study demonstrates the involvement of PKC in the brain in the regulation of the immobilization stress-induced stimulation of HPA axis in vivo.
Kim
D H
DH
Department of Psychiatry, College of Medicine, Hallym University, Chunchon, 200-702, Kangwon-Do, South Korea.
Jung
J S
JS
Kim
H S
HS
Suh
H W
HW
Son
B K
BK
Kim
Y H
YH
Song
D K
DK
D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology*; D002227:Carbazoles / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007103:Immobilization / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D051379:Mice; D008813:Mice, Inbred ICR; D009281:Naphthalenes / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology; D013312:Stress, Physiological / Q000503:physiopathology
D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D009281:Naphthalenes; C081021:Go 6976; D011493:Protein Kinase C; C058819:calphostin C; D003345:Corticosterone