G-protein inwardly rectifying potassium channels are involved in the hypotensive effect of I1-imidazoline receptor selective ligands.

OBJECTIVE: The 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. METHODS AND RESULTS: 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). CONCLUSION: 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.

[Not Available]. / Essais cliniques à Dakar : enquête sur les connaissances, attitudes et pratiques des principaux acteurs sur une période allant de 2003 à 2007.

AIM: The general objective of this study was to agree an inventory of fixtures of clinical trials done in Dakar, in order to make recommendations to improve the quality of clinical trials in Senegal. METHOD: We have done a survey from mars to may 2007, with investigators of the two biggest Senegalese university teaching hospitals and to the pharmacy management and the ethical committee. RESULTS: Our key results showed: 1) a small participation rate of teachers to clinical trials (11 on 37 interviewed); 2) that the principal sponsor is pharmaceutical industry; 3) that most of investigators have not degree in clinical trials; 4) that most pathologies concerned were malaria and AIDS; 5) that there are regulations related to clinical trials in Senegal. CONCLUSION: This study shows the necessity to integrate, in Senegal, clinical trials in the curricula of students training.