Galanin inhibits calcium channels via Galpha(i)-protein mediated by GalR1 in rat nucleus tractus solitarius.
Galanin (GAL), a 29-amino-acid neuropeptide, is involved in various neuronal functions, including the regulation of food intake, hormone secretion and central cardiovascular regulation. The nucleus tractus solitarius (NTS) is known to plays a major role in the regulation of cardiovascular, respiratory, gustatory, hepatic and swallowing functions. Voltage-dependent Ca2+ channels (VDCCs) serve as crucial mediators of membrane excitability and Ca(2+)-dependent functions such as neurotransmitter release, enzyme activity and gene expression. The purpose of this study was to investigate the effects of GAL on VDCCs currents (ICa) carried by Ba2+ (IBa) in the NTS using patch-clamp recording methods. An application of M617 (GalR1 specific agonist), AR-M961 (GAL receptor GalR 1/2 agonist) and GAL caused inhibition of N- and P/Q-types I(Ba). M617, GAL, and AR-M961 caused inhibition of I(Ba) in a concentration-dependent manner, with IC50s of 678 nM, 325 nM and 573 nM, respectively. This inhibition was relieved, albeit incompletely, by a depolarizing prepulse. Pretreatment with M35 (GalR non-specific antagonist) attenuated the M617-induced inhibition of I(Ba). Intracellular dialysis of the Galpha(i)-protein antibody also attenuated the Gal-induced inhibition of IBa. These results indicate that GAL inhibits N- and P/Q-types VDCCs via Galpha(i)-protein betagamma subunits mediated by GalR1 in NTS.
Endoh
Takayuki
T
Oral Health Science Center HRC7, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba 261-8502, Japan. tendoh@tdc.ac.jp
Sato
Daisuke
D
Wada
Yoshiyuki
Y
Shibukawa
Yoshiyuki
Y
Ishihara
Kazuyuki
K
Hashimoto
Sadamitsu
S
Yoshinari
Masao
M
Matsuzaka
Kenichi
K
Tazaki
Masakazu
M
Inoue
Takashi
T
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001464:Barium / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D044385:GTP-Binding Protein alpha Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019004:Galanin / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044091:Receptor, Galanin, Type 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D044385:GTP-Binding Protein alpha Subunits; D010446:Peptide Fragments; D044091:Receptor, Galanin, Type 1; C434733:galanin (1-16)-amide, Sar(1)-Ala(12)-; C074069:galanin-(1-13)-bradykinin-(2-9)-amide; D001464:Barium; D019004:Galanin; D001920:Bradykinin