Effects of the short chain sugar acid 2-buten-4-olide on the hypothalamo-pituitary-adrenal axis in normal and adjuvant-induced arthritic rats.
The effects of intraperitoneal (i.p.) administration of 2-buten-4-olide (2-B4O), an endogenous sugar acid, on the hypothalamo-adenohypophysial system were examined in Lewis rats that were normal and in adjuvant-induced arthritic (AA) rats. In comparison with vehicle-treated rats, the plasma corticosterone and c-fos mRNA levels in the paraventricular nucleus (PVN) of normal rats increased significantly after i.p. administration of 2-B4O. Dual immunostaining revealed that almost all corticotrophin-releasing factor (CRF)-immunopositive neurones in the parvocellular division of the PVN exhibited Fos-like immunoreactivity (LI) 120 min after i.p. administration of 2-B4O (100 mg/kg). In the AA rats, repeated i.p. administration of 2-B4O (100 mg/kg) after immunisation significantly suppressed the expression of clinical symptoms and significantly increased plasma concentrations of corticosterone. Further, repeated i.p. administration of 2-B4O significantly increased CRF mRNA levels in the PVN and pro-opiomelanocortin mRNA levels in the anterior pituitary; however, they did not change arginine vasopressin mRNA levels in the parvocellular division of the PVN. These results suggest that i.p. administration of 2-B4O activates the hypothalamo-pituitary-adrenal (HPA) axis via the activation of CRF neurones in the PVN, and the activation of the HPA axis by i.p. administration of 2-B4O may be associated with the inhibition of AA in rats.
Kawasaki
M
M
Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Onaka
T
T
Saito
J
J
Hashimoto
H
H
Suzuki
H
H
Otsubo
H
H
Fujihara
H
H
Okimoto
N
N
Ohnishi
H
H
Nakamura
T
T
Ueta
Y
Y
D015107:4-Butyrolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000276:Adjuvants, Immunologic; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000378:metabolism; D001169:Arthritis, Experimental / Q000097:blood / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
D000276:Adjuvants, Immunologic; D001067:Appetite Depressants; D016760:Proto-Oncogene Proteins c-fos; D001127:Arginine Vasopressin; C004511:butenolide; D003346:Corticotropin-Releasing Hormone; D015107:4-Butyrolactone; D003345:Corticosterone