mr-2266 and spiradoline
mr-2266 has been researched along with spiradoline* in 6 studies
Reviews
1 review(s) available for mr-2266 and spiradoline
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Kappa agonists and vasopressin secretion.
The effects of opiates on vasopressin secretion have been controversial for many years. This is probably due to the existence of different types of opioid receptors and to the lack of specificity of the compounds used. Specific kappa agonists, which have been described recently, produce a marked diuretic effect without any associated increase in electrolyte elimination. They seem to exert their effects through an interaction with kappa receptors situated on nerve terminals and/or pituicytes. These receptors could be directly coupled to L-type calcium channels, their activation leading to a decrease in the effectiveness of action potentials to evoke vasopressin secretion from nerve terminals in the neurohypophysis. This mechanism of action may explain the decrease in plasma vasopressin levels induced by kappa agonists. Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Benzomorphans; Diuretics; Paraventricular Hypothalamic Nucleus; Pyrrolidines; Rats; Receptors, Opioid; Receptors, Opioid, kappa; Supraoptic Nucleus; Vasopressins | 1990 |
Other Studies
5 other study(ies) available for mr-2266 and spiradoline
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kappa-Opioid receptor agonist protects against ischemic reduction of 2-deoxyglucose uptake in morphine-tolerant rats.
We examined the effects of mu-opioid receptor agonist and antagonists, and kappa-opioid receptor agonist on the hypoxia/hypoglycemia-induced reduction in 2-deoxyglucose uptake of rat hippocampal slices. Naloxone, a mu-opioid receptor antagonist and (5,7,8)-(+)-3,4-dichloro-N-methyl-N-(7,8,1-pyrrolidinyl)-1-oxaspirol+ ++ (4,5)dec-8-yl)-benzeneacetamide methanesulfonate, U-62,066E, a kappa-opioid receptor receptor agonist, showed neuroprotective actions against the hypoxia/hypoglycemia-induced deficit in glucose uptake. In contrast, morphine exhibited an exacerbating action. These results suggest that blockade of mu-opioid receptor- and stimulation of kappa-opioid receptor-mediated functions has a protective role against the hypoxia/hypoglycemia-induced decreases in glucose metabolism in hippocampal slices. Chronic administration of morphine (10 mg/kg) for 9 days affected neither the basal nor the hypoxia/hypoglycemia-induced reduction in 2-deoxyglucose uptake. Rats treated with morphine chronically exhibited not only tolerance to the analgesic effect but also tolerance to the exacerbating action. However, chronic morphine did not modify U-62,066E-induced neuroprotection. These findings indicate that the receptor mechanisms of neuroprotection produced by the activation of kappa-opioid receptors may not be involved in mu-opioid receptor function. Topics: Analgesics; Analgesics, Opioid; Animals; Benzomorphans; Brain Ischemia; Deoxyglucose; Drug Tolerance; Hippocampus; Hypoglycemia; Hypoxia, Brain; In Vitro Techniques; Male; Morphine; Naloxone; Narcotic Antagonists; Pyrrolidines; Rats; Rats, Wistar; Receptors, Opioid, kappa | 1995 |
Analgesic and discriminative stimulus properties of U-62,066E, the selective kappa-opioid receptor agonist, in the rat.
The analgesic and discriminative stimulus properties of U-62,066E, a selective kappa-opioid receptor agonist, were investigated in the rat and compared with those of morphine. In the hot-plate test, U-62,066E produced a potent analgesic effect almost comparable to that of morphine. U-62,066E-induced analgesia was far less sensitive to antagonism by naloxone than was morphine-induced analgesia, but was potently reversed by MR-2266, a kappa-receptor antagonist. Although tolerance occurred to both U-62,066E and morphine analgesia, there was no cross-tolerance between these drugs. U-62,066E did show cross-tolerance to U-50,488H, another selective kappa-receptor agonist. Rats were trained to discriminate either 1.0 mg/kg U-62,066E or 3.2 mg/kg morphine from saline in a two-level food-reinforced procedure. The stimulus effect of U-62,066E was substituted for by U-50,488H and E-2078 a stable dynorphin derivative, but not by morphine. None of the kappa-agonists substituted for the morphine stimulus. Although U-62,066E stimulus by itself was not antagonized by MR-2266 or naloxone up to as high a dose as 10 mg/kg, the U-62,066E-like stimulus effect of U-50,488H was markedly blocked by MR-2266. The dopamine antagonists haloperidol and sulpiride substituted for the U-62,066E stimulus cue that was, however, not attenuated by the dopamine agonist lisuride. Lisuride reversed the U-62,066E-like stimulus induced by U-50,488H.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Analgesics; Animals; Benzomorphans; Cues; Discrimination, Psychological; Dopamine; Dopamine Antagonists; Dynorphins; Male; Morphine; Narcotic Antagonists; Peptide Fragments; Pyrrolidines; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, kappa; Receptors, Opioid, mu | 1992 |
Atrial natriuretic polypeptide secretion via selective activation of kappa-opioid receptor: role of dynorphin.
The present study was designed to investigate the direct effect of dynorphin on atrial natriuretic polypeptide (ANP) secretion in cultured rat atrial cardiocytes via a kappa-opioid receptor activation as well as the involvement of adenosine 3',5'-cyclic monophosphate (cAMP) system in the secretion of ANP from cardiocytes. Dynorphin stimulated ANP secretion dose and time dependently from 2-day cultured atrial cardiocytes. The dynorphin-induced ANP secretion was partially antagonized by MR2266, a selective kappa-opioid receptor antagonist. U-62066E, a selective kappa-opioid receptor agonist, stimulated ANP secretion. This stimulation was also antagonized by MR2266. However, no stimulation of ANP secretion was seen with [D-Ala2,D-Leu5]enkephalin, methionine (Met)-enkephalin, or [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin. Dynorphin at 10(-6) M significantly decreased the production of cAMP in the cultured cardiocytes. However, 10(-6) M Met-enkephalin had no effect on cAMP at all. The decrease in cAMP production by the addition of dynorphin was partially antagonized with a simultaneous addition of MR2266. The dynorphin-induced ANP secretion, as well as the basal secretion, were significantly decreased by the addition of 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, as compared with the respective controls. Dibutyryl cAMP at 10(-3) M significantly decreased the basal secretion of ANP as compared with the control. Therefore, the present studies show that dynorphin selectively stimulates ANP secretion, at least in part, via the activation of a specific kappa-opioid receptor. Topics: 1-Methyl-3-isobutylxanthine; Animals; Animals, Newborn; Atrial Natriuretic Factor; Benzomorphans; Cells, Cultured; Diuretics; Dynorphins; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine-2-Alanine; Enkephalin, Methionine; Enkephalins; Heart; Heart Atria; Kinetics; Naloxone; Narcotic Antagonists; Pyrrolidines; Rats; Receptors, Opioid; Receptors, Opioid, kappa | 1991 |
Inhibition of elevated arginine vasopressin secretion in response to osmotic stimulation and acute haemorrhage by U-62066E, a kappa-opioid receptor agonist.
1. The effect of kappa (kappa) opioid receptor activation on the increase in arginine vasopressin (AVP) secretion evoked by two acute and quite different stimuli (i.e., haemorrhage and osmotic stimulus due to hypertonic saline infusion) were evaluated in conscious Long-Evans rats, by use of U-62066E, a highly selective kappa-opioid receptor agonist, and MR2266, an opioid receptor antagonist with some selectivity for kappa-receptors. 2. An acute haemorrhage, which reduced the mean blood pressure by approximately 50%, resulted in a large increase in the plasma AVP (pAVP) levels of control rats. However, the administration of U-62066E (0.2 mg kg-1 or 2.0 mg kg-1) reduced the increase due to haemorrhage in a dose-dependent manner. In contrast, concomitant administration of 2.0 mg kg-1 of MR2266 with U-62066E significantly attenuated the inhibition of pAVP levels produced by U-62066E 2.0 mg kg-1. 3. Hypertonic saline infusion (5% hypertonic saline solution at a rate of 0.24 ml kg-1 min-1 for 10 min) caused the elevation of plasma osmolality (pOsm) from 294.0 +/- 1.6 mosmol kg-1 to 304.4 +/- 1.9 mosmol kg-1, simultaneously resulting in a significant increase in pAVP levels from 2.34 +/- 0.28 pg ml-1 to 4.54 +/- 0.51 pg ml-1. However, the administration of U-62066E (0.05 mg kg-1 or 0.2 mg kg-1) reduced the osmotically induced increase in pAVP in a dose-dependent manner although pOsm showed the same degree of increase as in controls. In contrast, concomitant administration of 0.2mgkg-1 of MR2266 with U-62066E significantly attenuated the inhibition of pAVP levels produced by U-62066E 0.2mgkg- , whereas pOsm showed the same degree of increase as in controls. No significant changes in the mean blood pressure of the respective groups were observed during this experiment. 4. It is suggested that the Kappa-Opioid receptor activation reduces the increase in AVP secretion evoked by these two different stimuli and that the inhibitory involvement occurs in the neural lobe in the process of AVP secretion. Topics: Acute Disease; Analgesics; Animals; Arginine Vasopressin; Benzomorphans; Blood Pressure; Dose-Response Relationship, Drug; Hemorrhage; Hypertonic Solutions; Iodine Radioisotopes; Medulla Oblongata; Pyrrolidines; Rats; Receptors, Opioid; Receptors, Opioid, kappa | 1990 |
Mechanism of diuretic action of U-62,066E, a kappa opioid receptor agonist.
The mechanism of the diuretic action of U-62,066E, a highly selective kappa opioid agonist, was examined in unanesthetized rats and in isolated perfused inner medullary collecting ducts (IMCD). In Long-Evans rats, U-62,066E caused a dose-dependent increase in urine flow and a decrease in urine osmolality without affecting urinary excretion of Na+. The diuretic effect of U-62,066E was blocked by MR-2266, a kappa opioid receptor antagonist. U-62,066E showed no diuretic effect in homozygous hereditary diabetes insipidus rats (Brattleboro strain). In water-deprived rats, U-62,066E markedly inhibited plasma arginine vasopressin (AVP) levels through a kappa receptor-mediated mechanism. In rat IMCD perfused in vitro, 10(-5) M U-62,066E did not inhibit either the baseline or the AVP-stimulated osmotic water permeability. We conclude that the inhibition of the release of AVP is the major if not the entire mechanism of the diuretic action of U-62,066E in rats. Although we ruled out the effect of this drug on the water permeability of IMCD, possible direct effects on other nephron structures remain to be established. Topics: Animals; Arginine Vasopressin; Benzomorphans; Diuretics; In Vitro Techniques; Kidney Tubules, Collecting; Male; Narcotic Antagonists; Natriuresis; Osmolar Concentration; Pyrrolidines; Rats; Rats, Inbred BB; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, kappa | 1989 |