ici-199441 and norbinaltorphimine

The role of the central opioid system in the control of water and salt intake is complex, with both stimulatory and inhibitory effects having been observed. The aim of the present study was to investigate the participation of the central κ-opioid receptors in the control of salt appetite. Male Wistar rats were submitted to two different experimental protocols: sodium deficit produced by the diuretic, furosemide, and brain angiotensinergic stimulation in rats under normal sodium balance. Lateral ventricle (LV) injections of Nor-binaltorphimine (Nor-BNI) at different doses (5, 10 and 20 nmol) inhibited hypertonic saline solution (1.5%) intake in sodium-depleted rats. The salt appetite induced by an LV injection of angiotensin II (Ang II) (10 ng) was also blocked by Nor-BNI injections into the LV, while no significant change was observed in water intake. Furthermore, the decrease in salt intake seems not to have been due to a general inhibition of locomotor activity or to any change in palatability, since central administration of Nor-BNI failed to modify the intake of a 0.1% saccharin solution when the animals were submitted to a "dessert test" or to induce any significant locomotor deficit in the open-field test. Also the central administration of Nor-BNI was unable to modify blood pressure in sodium-depleted animals. The present results suggest that activation of endogenous κ-opioid receptors modulates salt appetite induced by sodium depletion and by central angiotensinergic stimulation in rats.

Topics: Angiotensin II; Animals; Appetite; Blood Pressure; Diuretics; Food Preferences; Furosemide; Injections, Intraventricular; Male; Microinjections; Motor Activity; Naltrexone; Narcotics; Pyrrolidines; Rats; Rats, Wistar; Receptors, Opioid, kappa; Signal Transduction; Sodium Chloride, Dietary

We investigated whether delta- and kappa-opioid agonists alter myocardial function, intracellular Ca(2+) concentration ([Ca(2+)](i)), and myofilament Ca(2+) sensitivity in intact guinea pig beating hearts and whether these effects are mediated by an opioid receptor. Intact guinea pig hearts were perfused with modified Krebs Ringer solution containing delta- (TAN-67) and kappa- (ICI-199441) opioid agonists in the absence and presence of delta- (BNTX) and kappa- (nor-BNI) opioid antagonists, respectively, while functional variables and [Ca(2+)](i) were recorded. TAN-67 (1 microM) and ICI-199441 (1 microM) decreased heart rate (P < 0.05). TAN-67 (1 microM) and ICI-199441 (1 micro M) decreased available [Ca(2+)](i) without changing developed left ventricular pressure (LVP) (P < 0.05). TAN-67 (1 microM) and ICI-199441 (1 microM) also caused a leftward shift in the curve of developed LVP as a function of available [Ca(2+)](i) (P < 0.05). ICI-199441 (1 microM) produced a steeper slope in the relation curve compared with baseline (P < 0.05). BNTX (1 microM) and nor-BNI (1 microM) blocked the effects of TAN-67 and ICI-199441, respectively. delta- and kappa-opioid agonists enhance myofilament Ca(2+) sensitivity despite decreasing available [Ca(2+)](i) in intact isolated guinea pig hearts, and these effects are mediated by delta- and kappa-opioid receptor stimulation.. Our results indicate that delta- and kappa-opioid agonists enhance myofilament Ca(2+) sensitivity despite decreasing available intracellular Ca(2+) concentrations in intact isolated guinea pig beating hearts, and these effects are mediated by delta- and kappa-opioid receptor stimulation.

Topics: Actin Cytoskeleton; Animals; Benzylidene Compounds; Blood Pressure; Calcium; Coronary Circulation; Guinea Pigs; Heart; Heart Rate; In Vitro Techniques; Kinetics; Naltrexone; Narcotic Antagonists; Pyrrolidines; Quinolines; Receptors, Opioid, delta; Receptors, Opioid, kappa; Stimulation, Chemical; Ventricular Function, Left