Pain threshold, learning and formation of brain edema in mice lacking the angiotensin II type 2 receptor.
The main biological role of angiotensin II type 2 receptor (AT2) has not been established. We made use of targeted disruption of the mouse AT2 gene to examine the functional role of the AT2 receptor in the central nervous system (CNS). We have previously shown that AT2-deficient mice displayed anxiety-like behavior in comparisons with wild-type mice. In the present study, we analyzed the pain threshold, learning behavior and brain edema formation using the tail-flick test, the tail-pinch test, the passive avoidance task and cold injury, respectively. In the passive avoidance task and cold injury, no differences were found between wild-type mice and AT2-deficient mice. In contrast, the pain threshold was significantly lower in AT2-deficient mice, compared with findings in wild-type mice. The immunohistochemical distribution of beta-endorphin in the brain was analyzed quantitatively in AT2-deficient mice and wild-type mice, using microphotometry. The fluorescence intensity of beta-endorphin in the arcuate nucleus of the medial basal hypothalamus (ARC) was significantly lower in AT2-deficient mice, compared with findings in wild-type mice. We found that the AT2 receptor does not influence learning behavior and brain edema formation. As AT2-deficient mice have increased sensitivity to pain and decreased levels of brain beta-endorphin, AT2 receptors may perhaps mediate regulation of the pain threshold.
Sakagawa
T
T
Laboratory of Animal Center, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., Ohmiya, Saitama, Japan.
Okuyama
S
S
Kawashima
N
N
Hozumi
S
S
Nakagawasai
O
O
Tadano
T
T
Kisara
K
K
Ichiki
T
T
Inagami
T
T
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D003080:Cold Temperature; D016650:Fluorescein-5-isothiocyanate; D006579:Heterozygote; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017288:Pain Threshold / Q000502:physiology*; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000172:deficiency / Q000502:physiology*; D013623:Tail; D001615:beta-Endorphin / Q000378:metabolism
D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D001615:beta-Endorphin; D016650:Fluorescein-5-isothiocyanate