Protein kinases are involved in prolonged acetylcholine release from rat hippocampus induced by thyrotropin-releasing hormone analogue NS-3.
The effects of various protein kinase inhibitors on acetylcholine release from the rat hippocampus induced by the local application of NS-3 (montirelin hydrate, CG-3703), a thyrotropin-releasing hormone analogue, into the medial septum-diagonal band were examined using in vivo microdialysis. Perfusion of NS-3 (1 microM) into the medial septum-diagonal band for 20 min produced a pronounced and prolonged increase in the hippocampal acetylcholine efflux. Pretreatment of the medial septum-diagonal band with either K-252a, a nonselective protein kinase inhibitor, or selective protein kinase A inhibitor H-89 almost completely blocked the acetylcholine efflux evoked by NS-3, and selective protein kinase C inhibitor calphostin C inhibited the action of NS-3. On the other hand, NS-3 (0.1-10 microM) or TRH (1-100 microM) increased the cyclic AMP efflux from the medial septum-diagonal band in a concentration-dependent manner, as measured by microdialysis. These findings suggest that protein kinases A and C in the neurons of the medial septum-diagonal band are involved in the mechanism of the prolonged stimulation of acetylcholine release from the hippocampus induced by thyrotropin-releasing hormone and its analogue, NS-3.
Oka
M
M
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Itoh
Y
Y
Ukai
Y
Y
Yoshikuni
Y
Y
Kimura
K
K
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D005625:Frontal Lobe / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D011494:Protein Kinases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012688:Septum Pellucidum / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
C031926:montirelin; D013973:Thyrotropin-Releasing Hormone; D011494:Protein Kinases; D000109:Acetylcholine