| Co-Investigator(Kenkyū-buntansha) |
UETA Yoichi Assistant University of Occupational and Environmental Health, 医学部, 助手 (10232745)
INENAGA Kiyotoshi Associate Professor University of Occupational and Environmental Health, 医学部, 助教授 (90131903)
MASSAKO KADE 米国, Univ Texas Medical Branch, 教授
KANNAN Hiroshi Professor Miyazaki Medical College, 医学部, 教授 (00049058)
KAWATA Mitsuhiro Professor Kyoto Prefectural University of Medicine, 医学部, 教授 (60112512)
KIYOMI KOIZU 米国, ニューヨーク州立大学・ブルックリン健康科学センター, 教授
KOIZUMI Kiyomi Professor State University of New York Health Science Center at Brooklyn
KADEKARO Masako Associate Professor University of Texas Medical Branch at Galveston
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| Research Abstract |
We investigated the central control mechanisms of drinking behavior and water homeostasis by study in the genetically polydipsic mouse, STR/N strain.
Immunocytochemical. molecular biological and metabolic studies of the brain revealed abnormal hyperactive vasopressin (AVP) and oxytocin (OXT) systems in the hypothalamus and abnormalities in the circumventricular organs of the ATR/N mouse, compared to the non-polydipsic control mouse. The polydipsia of the STR/N mouse was found to be attenuated somewhat by intracerebroventricular (icv) injections of angiotensin II (ANG-II) blockers, strongly attenuated by opioid antagonists (particularly k-receptor) and most effectively blocked by AVP antagonist, OPC-31260. Under Na^+ free diet drinking was strongly suppressed in the STR/N, but not in the control mouse. Neuron responses studied by electrophysiological techniques in grain slice preparations showed that the sensitivity to ANG-II of neurons in the subfornical organ and AV3V was not greatly different between the STR/N and its control mice. On the other hand, neuron responses to opioids were different. In the STR/N mouse neurons of the AV3V and paraventricular nucleus (PVN) were much less sensitive to opioids than those in the control mouse. The sensitivity of AV3V neurons to Na^+ was similar in both strains of mice. Measurement of AVP in the slice perfusate revealed a far greater release of AVP from the supraoptic nucleus and the PVN in the STR/N mouse compared to that in the control. These results suggest that in the polydipsic ATR/N strain of mouse hyperactive brain AVP-and OXT-systems, abnormalities in the brain angiotensin, opioid (particularly kappa-type) functions, and Na^+ sensitivity may all contribute its excessive drinking.
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