Involvement of α2-adrenoceptors, imidazoline, and endothelin-A receptors in the effect of agmatine on morphine and oxycodone-induced hypothermia in mice
3区 · 医学
作者: Bhalla, Shaifali ; Andurkar, Shridhar V. ; Gulati, Anil
Potentiation of opioid analgesia by endothelin-A (ET(A)) receptor antagonist, BMS182874, and imidazoline receptor/α₂-adrenoceptor agonists such as clonidine and agmatine are well known. It is also known that agmatine blocks morphine hyperthermia in rats. However, the effect of agmatine on morphine or oxycodone hypothermia in mice is unknown. The present study was carried out to study the role of α₂-adrenoceptors, imidazoline, and ET(A) receptors in morphine and oxycodone hypothermia in mice. Body temperature was determined over 6 h in male Swiss Webster mice treated with morphine, oxycodone, agmatine, and combination of agmatine with morphine or oxycodone. Yohimbine, idazoxan, and BMS182874 were used to determine involvement of α₂-adrenoceptors, imidazoline, and ET(A) receptors, respectively. Morphine and oxycodone produced significant hypothermia that was not affected by α₂-adrenoceptor antagonist yohimbine, imidazoline receptor/α₂ adrenoceptor antagonist idazoxan, or ET(A) receptor antagonist, BMS182874. Agmatine did not produce hypothermia; however, it blocked oxycodone but not morphine-induced hypothermia. Agmatine-induced blockade of oxycodone hypothermia was inhibited by idazoxan and yohimbine. The blockade by idazoxan was more pronounced compared with yohimbine. Combined administration of BMS182874 and agmatine did not produce changes in body temperature in mice. However, when BMS182874 was administered along with agmatine and oxycodone, it blocked agmatine-induced reversal of oxycodone hypothermia. This is the first report demonstrating that agmatine does not affect morphine hypothermia in mice, but reverses oxycodone hypothermia. Imidazoline receptors and α₂-adrenoceptors are involved in agmatine-induced reversal of oxycodone hypothermia. Our findings also suggest that ET(A) receptors may be involved in blockade of oxycodone hypothermia by agmatine.
2013-06-01·Endocrine, Metabolic & Immune Disorders: Drug Targets4区 · 医学
Combination of daidzein, hemin and Bms182874 halts the progression of diabetes-induced experimental nephropathy
4区 · 医学
作者: Katyal, Taruna ; Garg, Arun ; Budhiraja, R. D.
The present study has been designed to investigate the combined effect of daidzein (caveolin inhibitor), hemin (hemoxygenase activator) and BMS182874 (endothelin receptor antagonist) in diabetic nephropathy in wistar rats. Diabetic nephropathy was induced by administering single dose of streptozotocin in wistar rats. DN was clinically assessed by the estimation of various biochemical parameters and histopathological studies of renal tissue. DN was assessed by measuring serum creatinine, blood urea nitrogen, proteinuria, renal cortical collagen content, lipid profile, serum nitrite/nitrate ratio, renal TBARS and reduced glutathione levels. The combination of daidzein, hemin and BMS182874 showed significant improvement in (BUN, serum creatinine, proteinuria, urinary output, kidney weight/ body weight, renal cortical collagen content, nitrite/ nitrate level, renal TBARS, reduced glutathione) renal parameters studied for DN in comparison with single drug administration as well as a combination of two drugs. L-NAME (NG-nitro- L-arginine methyl ester) a selective eNOS inhibitor abolished the ameliorative effect of combination of daidzein, hemin and BMS182874 in DN in rats. It may therefore be concluded that Daidzein in combination with hemin may enhance the level of renal nitric oxide by decreasing the expression of caveolin. BMS182874 shows renoprotection by inhibiting RAAS system and through reactivation of NO synthesis. These findings may provide mechanistic insights to explain renoprotective effect of this combined therapy in diabetes.
2013-01-01·Pharmacology, Biochemistry and Behavior4区 · 心理学
Potentiation of oxycodone antinociception in mice by agmatine and BMS182874 via an imidazoline I2 receptor-mediated mechanism
The potentiation of oxycodone antinociception by BMS182874 (endothelin-A (ET(A)) receptor antagonist) and agmatine (imidazoline receptor/α(2)-adrenoceptor agonist) is well-documented. It is also known that imidazoline receptors but not α(2)-adrenoceptors are involved in potentiation of oxycodone antinociception by agmatine and BMS182874 in mice. However, the involvement of specific imidazoline receptor subtypes (I(1), I(2), or both) in this interaction is not clearly understood. The present study was conducted to determine the involvement of imidazoline I(1) and I(2) receptors in agmatine- and BMS182874-induced potentiation of oxycodone antinociception in mice. Antinociceptive (tail flick and hot-plate) latencies were determined in male Swiss Webster mice treated with oxycodone, agmatine, BMS182874, and combined administration of oxycodone with agmatine or BMS182874. Efaroxan (imidazoline I(1) receptor antagonist) and BU224 (imidazoline I(2) receptor antagonist) were used to determine the involvement of I(1) and I(2) imidazoline receptors, respectively. Oxycodone produced significant antinociceptive response in mice which was not affected by efaroxan but was blocked by BU224. Agmatine-induced potentiation of oxycodone antinociception was blocked by BU224 but not by efaroxan. Similarly, BMS182874-induced potentiation of oxycodone antinociception was blocked by BU224 but not by efaroxan. This is the first report demonstrating that BMS182874- or agmatine-induced enhancement of oxycodone antinociception is blocked by BU224 but not by efaroxan. We conclude that imidazoline I(2) receptors but not imidazoline I(1) receptors are involved in BMS182874- and agmatine-induced potentiation of oxycodone antinociception in mice.