Effects of vasopressin V1b receptor deficiency on adrenocorticotropin release from anterior pituitary cells in response to oxytocin stimulation.
Oxytocin (OT) is one of the secretagogues for stress-induced ACTH release. OT-induced ACTH release is reported to be mediated by the vasopressin V1b receptor in the rat pituitary gland, which contains both OT and V1b receptors. We examined OT-induced ACTH release using primary cultures of anterior pituitary cells from wild-type (V1bR+/+) and V1b receptor knockout (V1bR-/-) mice. OT stimulated similar levels of ACTH release from pituitary cells of V1bR+/+ and V1bR-/- mice. OT-induced ACTH release was significantly inhibited by the selective V1b receptor antagonist SSR149415 and the OT receptor antagonist CL-14-26 in V1bR+/+ mice. In addition, cotreatment with SSR149415 at 10(-6) m and CL-14-26 at 10(-6) m inhibited OT-induced ACTH release to the control level inV1bR+/+ mice. In V1bR-/- mice, OT-induced ACTH release was significantly inhibited by CL-14-26 at 10(-8) m and completely inhibited at 10(-7)m. These results indicate that OT induces the ACTH response via OT and V1b receptors inV1bR+/+ mice but via only OT receptors in V1bR-/- mice. The gene expression level of the OT receptor was significantly higher in the anterior pituitary gland of V1bR-/- mice than in that of V1bR+/+ mice, suggesting that the OT receptor is up-regulated to compensate for ACTH release under conditions of V1b receptor deficiency.
Nakamura
Kazuaki
K
Department of Pharmacology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.
Fujiwara
Yoko
Y
Mizutani
Reiko
R
Sanbe
Atsushi
A
Miyauchi
Noriko
N
Hiroyama
Masami
M
Yamauchi
Junji
J
Yamashita
Tatsuya
T
Nakamura
Shigeki
S
Mori
Toyoki
T
Tsujimoto
Gozoh
G
Tanoue
Akito
A
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010121:Oxytocin / Q000378:metabolism / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
C456029:1-(5-chloro-1-((2,4-dimethoxyphenyl)sulfonyl)-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl)-4-hydroxy-N,N-dimethyl-2-pyrrolidinecarboxamide; D007211:Indoles; D011759:Pyrrolidines; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D010121:Oxytocin; D000324:Adrenocorticotropic Hormone