Effects of cholecystokinin (CCK)-8 on hypothalamic oxytocin-secreting neurons in rats lacking CCK-A receptor.
Peripheral administration of cholecystokinin (CCK)-8 selectively activates oxytocin (OXT)-secreting neurons in the supraoptic (SON) and the paraventricular nuclei (PVN) with the elevation of plasma OXT level in rats. We examined the effects of intravenous (iv) administration of CCK-8 on the neuronal activity of hypothalamic OXT-secreting neurons and plasma OXT level in Otsuka Long-Evans Tokushima Fatty (OLETF) rats that have a congenital defect in the expression of the CCK-A receptor gene. In situ hybridization histochemistry (ISH) for c-fos mRNA revealed that the expression of the c-fos gene was not induced in the SON, the PVN, the nucleus of the tractus solitarius (NTS) and the area postrema (AP) 30 min after iv administration of CCK-8 (20 and 40 microg/kg) in OLETF rats. In Long-Evans Tokushima Otsuka (LETO) rats (controls), c-fos mRNA was detected abundantly in those nuclei 30 min after iv administration of CCK-8 (20 microg/kg). Immunohistochemistry for c-fos protein (Fos) showed that the distributions of Fos-like immunoreactivity (LI) were identical to the results obtained from ISH. Dual immunostaining for OXT and Fos revealed that Fos-LI was mainly observed in OXT-secreting neurons in the SON and the PVN of LETO rats 90 min after iv administration of CCK-8 (20 microg/kg). Radioimmunoassay for OXT and arginine vasopressin (AVP) showed that iv administration of CCK-8 did not cause significant change in the plasma OXT and AVP levels in OLETF rats, while iv administration of CCK-8 caused a significant elevation of plasma OXT level without changing the plasma AVP level in LETO rats. These results suggest that peripheral administration of CCK-8 may selectively activate the hypothalamic OXT-secreting neurons and brainstem neurons through CCK-A receptor in rats.
Hashimoto
Hirofumi
H
Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Onaka
Tatsushi
T
Kawasaki
Makoto
M
Chen
Lei
L
Mera
Takashi
T
Soya
Atsushi
A
Saito
Takeshi
T
Fujihara
Hiroaki
H
Sei
Hiroyoshi
H
Morita
Yusuke
Y
Ueta
Yoichi
Y
D000818:Animals; D030801:Animals, Genetically Modified; D001127:Arginine Vasopressin / Q000097:blood; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D002766:Cholecystokinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects*; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D016761:Oncogene Proteins v-fos / Q000235:genetics / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D020334:Rats, Inbred OLETF; D043886:Receptor, Cholecystokinin A / Q000172:deficiency*; D013997:Time Factors; D000099153:Pentraxins
D001127:Arginine Vasopressin; D002097:C-Reactive Protein; D002766:Cholecystokinin; D009419:Nerve Tissue Proteins; D016761:Oncogene Proteins v-fos; D010121:Oxytocin; D010446:Peptide Fragments; D043886:Receptor, Cholecystokinin A; D000099153:Pentraxins; C410885:cholecystokinin 8