Lack of trimethyltin (TMT)-induced elevation of plasma corticosterone in PACAP-deficient mice.
Accumulating evidence implicates pituitary adenylate cyclase-activating polypeptide (PACAP) in a number of stress responses. By using PACAP-deficient mice, PACAP has been shown to have an in vivo role in the regulation of the sympathoadrenal axis, but a role in regulating the hypothalamo-pituitary-adrenal (HPA) axis has not been fully addressed. To elucidate the role of endogenous PACAP in HPA axis regulation during pathological conditions, mice lacking the Adcyap1 gene encoding the neuropeptide PACAP (Adcyap1-/-) were injected with trimethyltin (TMT), a neurotoxin known to induce neuronal damage and several systemic responses including elevated plasma corticosterone levels. In wild-type controls, TMT induced transient decreases in water and food intake, with a concomitant decrease in body weight; however, no significant changes were observed in Adcyap1-/- mice. Basal corticosterone levels were not significantly different between the mutant and wild-type mice. TMT induced a marked elevation of plasma corticosterone above basal levels in wild-type mice but no significant increase was seen in Adcyap1-/- mice. The present article suggests that PACAP is involved in the corticosterone release in some pathological conditions but not in the basal state.
Morita
Yoshiko
Y
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Yanagida
Daisuke
D
Shintani
Norihito
N
Ogita
Kiyokazu
K
Nishiyama
Norito
N
Tsuchida
Rie
R
Hashimoto
Hitoshi
H
Baba
Akemichi
A
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood*; D004435:Eating / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D014298:Trimethyltin Compounds / Q000494:pharmacology*; D014867:Water / Q000378:metabolism
C495402:Adcyap1 protein, mouse; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014298:Trimethyltin Compounds; D014867:Water; C046488:trimethyltin; D003345:Corticosterone