Guata Yoro Sy, Dragan Urosevic, Lyne Fellmann, Hugues Greney, Pascal Bousquet, Josiane Feldman
Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, INSERM U715, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Journal of hypertension 2008 MayThe present study examined the role of G-protein inwardly rectifying potassium (GIRK) channels in the depressor responses elicited by intracisternal injections of imidazoline-like drugs in anesthetized rabbits. Intracisternal injections of the I1-imidazoline receptor (I1R) selective ligands LNP509 (30 microg/kg) and LNP640 (2 microg/kg) (subthreshold doses), and of the GIRK channel opener flupirtine (30 microg/kg) did not affect mean arterial blood pressure (MAP). LNP509 and LNP640, however, elicited substantial depressor responses in rabbits pretreated with flupirtine (-17 +/- 2 and -18 +/- 1 mmHg, respectively, P < 0.05). Injection of higher doses of LNP509 (200 microg/kg) or LNP640 (10 microg/kg) elicited substantial reductions in MAP (-45 +/- 3 and -39 +/- 2 mmHg, respectively, P < 0.05) in naive rabbits. The depressor responses elicited by the higher doses of LNP509 or LNP640 were markedly diminished by pretreatment with the GIRK channel blocker tertiapin-Q (10 microg/kg) (-23 +/- 3 and -26 +/- 2 mmHg, respectively, P < 0.05 compared with nonpretreated rabbits), whereas tertiapin-Q (10 microg/kg) did not affect MAP by itself. Maximal-specific binding (Bmax) of the I1R ligand [I]LNP911 to PC12 cell membranes (296 +/- 59 fmol/mg protein) was enhanced by flupirtine pretreatment whereas it was reduced by tertiapin-Q pretreatment (687 +/- 122 and 68 +/- 21 fmol/mg protein, respectively, P < 0.05 vs. control binding). These findings demonstrate that the modulation of GIRK channels affects I1R's function and raise the possibility that GIRK channels, and I1Rs are parts of a single proteic complex.
Guata Yoro Sy, Dragan Urosevic, Lyne Fellmann, Hugues Greney, Pascal Bousquet, Josiane Feldman. G-protein inwardly rectifying potassium channels are involved in the hypotensive effect of I1-imidazoline receptor selective ligands. Journal of hypertension. 2008 May;26(5):1025-32
PMID: 18398346
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