Kappa-opioid-receptor agonists modulate the renal excretion of water and electrolytes in anaesthetized rats.

1. Subcutaneous injection of the kappa-opioid agonists U50,488 (10 mg kg-1) and tifluadom (3.5 mg kg-1) into Inactin-anaesthetized, saline-infused rats was associated with a diuresis, antinatriuresis and antikaliuresis which lasted for up to 2 h. A high (5 mg kg-1), but not low (0.1 mg kg-1), dose of naloxone blocked the renal effects of U50,488. 2. U50,488 administration in anaesthetized, vasopressin-deficient Brattleboro DI rats was associated with an attenuated diuresis, though the antinatriuretic response remained intact. 3. The diuretic action of U50,488 was associated with an increase in glomerular filtration rate while fractional fluid reabsorption remained steady. In contrast, fractional sodium and potassium reabsorption were increased. 4. These data suggest that kappa-opioid agonists alter renal handling of both water and electrolytes. This appears to be mediated by two separate mechanisms: increased fluid loss largely reflects altered glomerular events while the fall in electrolyte excretion results from altered tubular handling.     

Effects of V2-receptor antagonist tolvaptan and the loop diuretic furosemide in rats with heart failure

Diuretics are frequently required to treat fluid retention in patients with chronic heart failure (CHF). Unfortunately, they can lead to a decline in renal function, electrolyte depletion, and neurohormonal activation. Arginine vasopressin (AVP) promotes renal water reabsorption via the V(2) receptor (V(2)R) and its levels are increased in CHF. This study was conducted to characterize the diuretic effect of tolvaptan, a non-peptide AVP V(2)R antagonist, and furosemide, a loop diuretic in a rat model of CHF after experimental autoimmune myocarditis. CHF was elicited in Lewis rats by immunization with porcine cardiac myosin, and 28 days after immunization rats were treated for 28 days with oral tolvaptan, and furosemide. CHF was characterized by left ventricular remodeling and impaired systolic and diastolic function. Tolvaptan produces a diuresis comparable to furosemide. Unlike tolvaptan, furosemide significantly increased urinary sodium and potassium excretion. Tolvaptan markedly elevated electrolyte-free water clearance (E-CH(2)O) or aquaresis to a positive value and increased urinary AVP excretion. In contrast to tolvaptan, furosemide elevated only electrolyte clearance (E-Cosm) but not E-CH(2)O. The differences in diuretic profile reflected the changes in plasma sodium and hormone levels. Tolvaptan dose dependently elevated plasma sodium concentration, but furosemide tended to decrease it. Furosemide significantly elevated plasma renin activity and aldosterone concentration. On the other hand, tolvaptan did not affect these parameters. Our results suggest that, tolvaptan have a potential medical benefit for the treatment of edematous conditions in CHF by removing excess water from the body without activating the RAAS or causing serum electrolyte imbalances.     

On the mechanisms of kappa-opioid-induced diuresis

In conscious saline loaded rats, the kappa-opioid agonists tifluadom, U50488, and ethylketocyclazocine, given subcutaneously, induced a characteristic diuresis which could be antagonized by naloxone. Bilateral adrenal demedullation significantly reduced adrenal gland catecholamine content and plasma adrenaline levels, but did not significantly affect plasma corticosterone levels, indicating that the adrenal cortex remained both intact and functional. Seven days following bilateral adrenal demedullation, the subcutaneous administration of the kappa-agonists no longer induced diuresis. However, demedullation did not affect the diuretic response to frusemide or clonidine, nor did it affect the antidiuretic response induced by the mu-opioid agonists morphine and buprenorphine. Adrenal catecholamines do not appear to be involved in kappa-opioid-induced diuresis, since pretreatment with propranolol, prazosin and idazoxan did not affect the diuretic response in intact animals. The results indicate a link between the adrenal medulla and kappa-opioid-induced diuresis and suggest that a peripheral mechanism may also be involved in mediating this effect.     

Central and peripheral actions of alpha 2-adrenergic agonists on renal function in Long-Evans and Brattleboro rats

The effects of 3 alpha 2-adrenergic receptor agonists on renal function in vasopressin (AVP)-deficient Brattleboro (DI) rats were evaluated. The aim of this study was to determine the relative contribution of central versus peripheral alpha 2-adrenoceptors in mediating diuresis and natriuresis, as well as the role of alpha 2-adrenoceptors in antagonizing the actions of AVP. In addition to the studies of renal function, the effects of AVP deficiency on renal alpha 2-adrenoceptor affinity and number was evalauted along with determination of peripheral catecholamine stores. The centrally acting alpha 2-adrenergic agonists guanabenz and guanfacine significantly increased urine output and sodium excretion in Long-Evans (LE) rats. Guanabenz and guanfacine increased urine output in DI rats but failed to increase sodium excretion. The polar alpha 2-adrenergic agonist, ST-91, increased sodium excretion in both LE and DI rats, however, at a dose of 1.0 mg/kg urine output was significantly decreased in DI rats. The 3 alpha 2-adrenergic agonists increased potassium excretion in LE rats, but at the 1.0-mg/kg dose of guanabenz and ST-91, potassium excretion was significantly inhibited in DI rats. Renal alpha 2-adrenergic receptors and norepinephrine stores were not altered in DI rats. Adrenal NE stores were significantly elevated in DI rats relative to LE rats. The results of this study suggest that in the absence of AVP, centrally acting alpha 2-adrenergic agonists have limited natriuretic action, although peripheral activation of alpha 2-adrenoceptors is sufficient to elicit natriuresis irrespective of the presence of AVP. The chronic deficiency of AVP does not alter renal alpha 2-adrenergic receptor number, but the natriuretic and kaliuretic actions of alpha 2-adrenergic agonists are altered in DI rats.     

Effect of arginine vasopressin on urine formation and plasma atrial natriuretic peptide level in conscious dogs

We investigated the relationship between plasma arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) levels and urine formation in conscious dogs. The rate of urine production and urinary electrolyte excretion were determined following infusion of high doses of AVP to dogs in different volume states. Water deprivation for 24 h induced an antidiuresis while the plasma osmolality, plasma AVP and plasma ANP remained at physiological levels. Subsequent i.v. administration of AVP did not alter the production of urine. Oral water loading (20 ml/kg body weight) induced low plasma AVP levels (1.3 +/- 0.5 pg/ml, mean +/- S.E.M.). Following AVP administration to the water-loaded group, the urine production rate decreased significantly from baseline while the osmolality of the urine increased significantly. Plasma ANP levels did not differ significantly between the two experimental groups, and did not change following i.v. administration of AVP. The results show that, in conscious dogs, (1) the production of a small volume of highly concentrated urine can occur with plasma AVP levels of below 5 pg/ml, (2) 24 h of dehydration induces an antidiuresis while plasma peptides, as well as the different biochemical variables, remain within normal limits, (3) increased plasma AVP levels do not induce a change in plasma ANP levels under these experimental conditions, (4) infusion of AVP induces a significantly increased K+ excretion but only in overhydrated animals.     

Renal electrolyte and fluid handling in the rat following chloroquine and/or ethanol administration

We postulated that chloroquine and/or ethanol affect plasma arginine vasopressin (AVP) concentrations to alter renal function. Therefore, we studied the effects of chloroquine and/or ethanol on plasma AVP concentrations and fluid, urinary Na(+) and K(+) outputs in separate groups of anaesthetized Sprague-Dawley (SD) rats challenged with a continuous jugular infusion of 0.077 M NaCl at 150 microl.min(-1). After a 3-h equilibration period, vehicle, chloroquine (0.06 microg. min(-1)), ethanol (2.4 or 24 microg.min(-1)) or both chloroquine and ethanol were added to the infusate after 1 h (control) for 1 h 20 min (treatment). The animals were switched back to the infusate alone for the final 1 h 40 min recovery periods. Urine flow Na(+) and K(+) excretion rates were determined at 20-min intervals over the subsequent 4-h postequilibration period. Blood was collected from separate groups of animals at the end of treatment period or equivalent time for control animals for measurement of plasma aldosterone and AVP concentrations by radioimmunoassay. Simultaneous chloroquine and ethanol infusion significantly (p < 0.01) increased plasma chloroquine concentrations in an ethanol dose-dependent manner by comparison with animals administered chloroquine alone. Chloroquine infusion alone (0.06 microg.min(-1)) and/or ethanol (2.4 or 24 microg.min(-1)) elevated plasma AVP concentrations from 9.73 +/- 1.64 fmol.l(-1) in control rats to 15.65 +/- 2.49 fmol.l(-1), 17. 39 +/- 4.21 fmol.l(-1), and 33.87 +/- 6.18 fmol.l(-1), respectively. Separate administration of chloroquine or ethanol at low dose rates increased urinary Na(+) excretion rates. We conclude that the impairment of renal electrolyte handling associated with chloroquine administration may be exacerbated by ethanol.     

Central administration of kisspeptin-lO inhibits natriuresis and diuresis induced by blood volume expansion in anesthetized male rats

Aim:

To investigate the possible role of hypothalamic kisspeptin in the regulation of body fluid metabolism and maintenance of internal homeostasis.

Methods:

Natriuresis and diuresis were induced by blood volume expansion (VE) in anesthetized male rats and kisspeptin-10 was intracerebroventricularly (icv) administered. Radioimmunoassay (RIA) was used to measure the plasma arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) concentrations during the VE. The mediation of the renal sympathetic nerve was also investigated in rats with bilateral renal sympathetic denervation.

Results:

The increased urine flow and sodium excretion induced by VE were significantly inhibited by icv injection of 5 nmol kisspeptin-10 (P<0.05), which peaked 20 min after the decrease in VE. The mean arterial blood pressure and heart rate did not change during the experiment. Plasma AVP concentrations were significantly increased 20 min after icv injection of 5 nmol kisspeptin-10 during VE (P<0.05), while pretreatment with 5 nmol kisspeptin-10 did not significantly change plasma ANP concentrations. Furthermore, pretreatment with 5 nmol kisspeptin-10 could significantly inhibit VE-induced natriuresis and diuresis in renal sympathetic denervated rats (P<0.05).

Conclusion:

Central administration of kisspeptin-10 inhibited VE-induced natriuresis and diuresis. This effect was likely mediated by increasing AVP release independent of plasma ANP concentration and renal sympathetic nerve activity.     

Clonidine-induced increase of renal prostaglandin activity and water diuresis in conscious dogs.

I.v. administration of clonidine to conscious dogs induces a water diuresis with hyposmotic urine and minor effect on electrolyte excretion. The diuresis is preceded by an increased urinary PGE excretion, but no change of urinary ADH output is observed. Plasma renin activity decreases. Both ADH infusion and indomethacin pretreatment inhibit the diuretic effect of clonidine. The results support the hypothesis that clonidine-induced water diuresis is mediated via an anti ADH effect due to increased renal prostaglandin activity. Moreover the results suggest that there is no direct stimulation of renin release by PGE.     

Chronic administration of U50,488H fails to produce hypothalamo-pituitary-adrenal axis tolerance in neonatal rats.

The present study investigated the effect of chronic administration of a kappa opioid receptor agonist on the function of kappa and mu opioid, serotonergic and cholinergic regulation of secretion from the hypothalamo-pituitary-adrenal axis in neonatal rats. After chronic treatment with saline or U50,488H (trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]- benzeneacetamide methane sulfonate), a kappa opioid receptor agonist and subsequent pharmacological challenge, corticosterone (CS) in serum was determined. Kappa tolerance did not develop in pups treated on postnatal days 5-9 with increasing doses of U50,488H (0.5-2.5 mg/kg). When the rats were treated with the same chronic regimen of U50,488H at different stages of development from birth through weaning, only weanling rats became tolerant to U50,488H. In the absence of measurable kappa tolerance, the responses of corticosterone in serum to morphine, quipazine, a serotonin receptor agonist and physostigmine, an inhibitor of acetylcholinesterase, were attenuated in neonatal rats, treated with U50,488H. These studies suggest that kappa tolerance is more difficult to induce in developing rats than in adults and that regulation of the function of the hypothalamo-pituitary-adrenal axis by other neurotransmitter systems is altered by treatment with kappa opioid receptor agonists, even in the apparent absence of tolerance.     

Taurine modulates arginine vasopressin-mediated regulation of renal function

Taurine has been implicated in the regulation of arginine vasopressin (AVP) secretion, and we have previously shown altered renal excretory function in the taurine-depleted rat. To further elucidate the role of taurine in AVP-mediated renal responses, the effects of an antagonist for renal AVP receptors were examined in four groups of conscious rats: control, taurine-supplemented, taurine-depleted, and taurine-repleted. Control and taurine-supplemented rats displayed similar and significant AVP receptor antagonist-induced elevations in fluid excretion, sodium excretion, and free water clearance but a marked reduction in urine osmolality. These effects are consistent with inhibition of endogenous AVP activity. By contrast, in the taurine-depleted rats, the magnitude and the time course of drug-induced renal excretory responses lagged behind those of the control and taurine-supplemented groups. Further, baseline urine osmolality was significantly higher in the taurine-depleted compared with the control or taurine-supplemented groups. However, after administration of the antagonist, taurine-depleted rats manifested a delayed but more marked reduction in urine osmolality, thereby eliminating the baseline differential that existed between the taurine-depleted rats and control or taurine-supplemented groups. Consistent with these observations, plasma AVP was significantly increased in the taurine-depleted compared with the control rats. Interestingly, taurine repletion shifted all responses closer to the control group. Analysis of the data suggests that the effect of the antagonist on renal excretory function is related primarily to altered tubular reabsorption activity. These observations suggest that taurine modulates renal function, and, thereby, body fluid homeostasis, through an AVP-dependent mechanism.     

No evidence for a physiological coupling between melatonin and glucocorticoids

Much has been speculated about the existence of a physiological coupling between melatonin and glucocorticoid secretion and about a possible anti-stress action of melatonin. We examined the relationship between melatonin and glucocorticoid secretion under close-to-physiological conditions, when the plasma concentration of either melatonin or glucocorticoids was elevated acutely or chronically in both rats and humans. Tryptophan administration caused a massive rise of plasma melatonin, but had no effect on corticosterone levels in rats or on cortisol levels in humans. The acute and long-lasting exposure of rats to uncontrollable stress resulted in a significant rise of adrenal corticosterone secretion, but had no effect on circulating melatonin levels. Orchectomy caused an initial increase in circulating corticosterone (when melatonin was unaffected) and a delayed rise in circulating melatonin (when corticosterone levels were normalized). In humans, no correlation was found between the nocturnal urinary excretion of melatonin and cortisol, either among healthy subjects, or among patients suffering from panic disorder (with an increased urinary excretion of cortisol) or among insomnia patients (with a high incidence of low melatonin secretion). Furthermore, no evidence was found for a suppressive action of melatonin on dexamethasone-mediated thymus regression in rats and on dexamethasone-mediated suppression of lymphocyte proliferation in vitro. Taken together, the results of this study provide no evidence for the existence of mutual influences between melatonin and glucocorticoid secretion, nor do they support the proposed attenuation of glucocorticoid-mediated effects on target cells or tissues by melatonin under physiological conditions. Received: 25 July 1996/Final version: 21 May 1997     

The effect of adrenal demedullation on cardiovascular responses to environmental stimulation in conscious rats.

Circulating plasma adrenaline has been implicated in the facilitation of neurogenic pressor responses and development of hypertension. Bilateral adrenal demedullation in rats did not affect body weight, urine output, urinary electrolyte (Na+, K+ and Cl-) excretion, nor plasma corticosterone concentration, indicating the selective nature of the demedullation procedure. Adrenal demedullation did induce significant reductions in adrenal catecholamine content, plasma adrenaline levels, resting blood pressure and heart rate in conscious rats, but did not affect alerting-induced increases in blood pressure. The adrenal medulla and circulating plasma adrenaline appear to contribute to the maintenance of resting cardiovascular parameters, but would not appear to be involved in nor facilitate the cardiovascular responses to environmental stimulation.     

ACUTE EFFECT OF ETHANOL ON RENAL ELECTROLYTE TRANSPORT IN THE RAT

1. Despite human and animal studies, the direct effect of ethanol on renal water and electrolyte transport is poorly understood. The acute effect of increasing plasma concentrations of ethanol was evaluated in a water diuretic anaesthetized rat model which inhibits endogenous arginine vaso-pressin (AVP) release. 2. Ethanol at a plasma concentration of 1.69 ±0.28 mmol/L produced an immediate increase in urine flow (174 ± 11 μL/min pre-ethanol and 189 ± 13 and then 206 ± 12 μL/min during the ethanol infusion; P<0.001) as well as an increase in fractional sodium excretion (0.17 ± 0.04 to 0.28 ± 0.05 and 0.27 ± 0.05%; P<0.001). There was also a brief phosphaturia. These increases in electrolyte excretion had returned to control values by 20 min despite a further increase in the plasma ethanol concentration. 3. The urinary excretion of potassium, calcium and magnesium was not altered nor was glomerular filtration rate or renal plasma flow. 4. Ethanol at a mean concentration of 1.60 mmol/L did not alter the action of a maximal concentration of AVP (75 ng/kg) on water or electrolyte transport. However, the antidiuretic effect of a submaximal concentration of AVP (7.5 ng/kg) was augmented by ethanol at concentrations of 1.63 and 0.98 mmol/L. 5. These studies suggest that the ethanol induced diuresis commonly ascribed to inhibition of AVP secretion may also be due to other intrarenal effects of ethanol, possibly acting within the proximal tubule. These results also confirm recent in vitro findings that while ethanol does not inhibit the action of a maximal concentration of AVP, it does modulate the effects of lower AVP concentrations.     

Renal response to blood volume expansion in Brattleboro rats after acute treatment with vasopressin

Summary The renal response to iso-oncotic blood volume expansion with bovine serum albumin was studied in anaesthetized homozygous Brattleboro (DI) rats after acute (1 day) pretreatment with 1 U arginine-vasopressin (AVP) compared to heterozygous controls. In AVP-treated DI (DI+AVP) rats, basal urine flow as well as urinary sodium, chloride, and potassium excretion, were not different from controls.Diuresis and kaliuresis induced by volume expansion were blunted in DI+AVP rats. However, natriuresis and chloruresis were exaggerated in DI+AVP rats. They increased faster, reached a higher maximum, but declined earlier, compared to controls. The blunted diuresis resulted in a positive volume balance by the end of the experiment in DI+AVP rats, whereas the controls showed restoration of normal balance. Significant retention of sodium and chloride was observed in controls, but not in DI+AVP rats, over the time of the experiment.DI+AVP rats lost significantly less potassium than controls during the experiment. As judged from the lithium clearance method, the exaggerated saluresis in DI+AVP rats was mainly due to a reduced proximal sodium reabsorption. Plasma immunoreactivity of atrial natriuretic peptide (ANP) rose during blood volume expansion and fell in the recovery period. It was not different between AVP-treated DI rats and controls at any time of the experiment. Inulin clearance was slightly, but not significantly, lower in DI+AVP rats and increased after blood volume expansion in DI+AVP rats only.The results indicate that acute AVP substitution may abolish the exaggerated volume loss, but not the increased saluresis known to occur in DI rats after blood volume expansion. Send offprint requests to R. Palluk at the above address     

The influence of tetracosactide and adrenal steroids on renal kallikrein activity and urinary kallikrein excretion in rats

The effect of adrenal steroids (mineralo- and glucocorticoids) as well as that of the adrenocorticotrophic peptide tetracosactide (beta 1-24 corticotropin) on the renal kallikrein activity and on the urinary kallikrein excretion of rats was investigated. After the animals had been adapted to metabolic cages, they were injected with deoxycorticosterone acetate (15 mg/kg day), corticosterone (40 mg/kg day), both steroids combined or the vehicle (sesame oil). Additional groups of rats received tetracosactide (0.05, 0.1 or 0.2 mg/day) or the vehicle (100 microliter of 38 X 10(-3) M ZnCl2). After four days of treatment the urinary kallikrein excretion was higher in deoxycorticosterone-treated rats than in their controls. This increase was prevented when corticosterone was administered simultaneously. The renal kallikrein activity of corticosterone as well as that of deoxycorticosterone plus corticosterone-treated rats was subnormal. A dose-related reduction of both the renal kallikrein activity and the urinary kallikrein excretion was observed 2 days after starting the tetracosactide administration. It may be concluded that a stimulation of the endogenous release of glucocorticoids in the rat reduces the renal kallikrein activity and that glucocorticoids can prevent the stimulating effect of mineralocorticoids.     

Regional rat brain noradrenaline turnover in response to restraint stress

Male Wistar rats were starved for 12 hr and then subjected to either 2 hr of wire mesh “envelope” restraint at room temperature; 2 hr of supine restraint in a specially constructed harness at room temperature or were not restrained. Eight brain regions were examined for NA level and the level of its major metabolite, MHPG-SO₄. Plasma corticosterone and gastric ulcer incidence were also measured. All restrained rats displayed marked elevations in MHPG-SO₄ levels in most brain regions. In addition, several brain regions in restrained animals showed a reduction in NA level. All restrained rats showed elevated plasma corticosterone levels and evidence of gastric lesions. In general, supine restraint produced greater alterations in regional brain NA turnover, greater evidence of ulcer disease, and higher plasma corticosterone levels than did wire mesh restraint. These data suggest that acute but intense stress in the form of restraint causes markedly altered brain NA activity—a possible neurochemical mechanism underlying the phenomenon of stress-induced disease.     

Studies on the pharmacology of central opioid-induced increases in plasma catecholamines in conscious rats

Centrally-administered opioid peptides produce elevations in levels of catecholamines in plasma in conscious rats. To investigate the opioid receptor involved in mediating this response, morphine (3.5-105 nmol), [D-Ala2-D-Leu5]enkephalin (DADL, 1.05-35 nmol) and U50, 488H (35-1160 nmol), relatively selective ligands for the mu, delta and kappa receptors respectively, were injected intracerebroventricularly into conscious rats and the levels of catecholamines in plasma determined at the peak of the response. Each agonist produced dose-dependent elevations in levels of noradrenaline and adrenaline, the order of potency being DADL approximately equal to morphine greater than U50,488H. These results exclude involvement of the kappa receptor but do not distinguish between an effect mediated by a mu or delta receptor. The responses to morphine were blocked in the presence of 300 nmol naloxone but were not altered by 41.5 nmol RX 781094, a selective alpha 2-adrenoceptor antagonist. The elevation in levels of adrenaline in plasma produced by small doses of the agonists was not related to behavioural changes.     

Effect of osmotic diuresis on gentamicin-induced nephrotoxicity in rats

The effect of isosorbide diuresis on gentamicin excretion and tissue accumulation as well as gentamicin-induced histopathologic changes in renal tissue were examined in rats. Gentamicin (30, 60, 120, 160 mg/kg) was administered s.c. for 10 consecutive days with or without isosorbide pretreatment. Osmotic diuresis with isosorbide did not significantly reduce the dose-dependent extent of gentamicin accumulation in renal tissues in comparison to nondiuresed rats. Although the urinary concentration of gentamicin was reduced in the diuresed animals, total gentamicin excretion remained unaffected. In addition, diuresis altered neither the renal excretion of the proximal tubular cell marker enzyme, N-acetyl-B-glucosaminidase, nor the severity of pathologic damage as determined by light microscopic examination of renal tissues. It appears that osmotically-induced diuresis alone is insufficient to prevent or significantly reduce gentamicin nephrotoxicity in rats. This is in contrast to other forms of diuretic therapy, such as furosemide, which have been shown to effectively reduce renal accumulation and resultant renal toxicity of aminoglycoside administration.     

氧氟沙星在肾功能障碍大鼠唾液中的分布

目的 :研究肾功能障碍时氧氟沙星 (OFLX)在唾液中分布的变化规律。方法 :通过 5 / 6肾摘除术 ,制成大鼠肾功能障碍模型 ,以模拟手术为对照。OFLX( 10mg·kg-1)静脉注射后 ,经时采血及腮腺 (Pr)、颌下腺 (M )唾液。采用HPLC法测定各样品中的OFLX浓度。结果 :肾功能障碍使大鼠OFLX血浆浓度显著增高 ,全身清除率下降约 4 0 %。肾障碍组Pr唾液中浓度明显增高 ,而M唾液中浓度与对照组之间差异无显著性。在肾功能障碍组及对照组 ,消失相的OFLX唾液中浓度及唾液 /血浆浓度比 (S/P比 ) ,在Pr唾液均比M唾液高约 2和 3倍。肾功能正常大鼠的S/P比与Pr唾液中药物浓度之间呈良好正相关。结论 :OFLX在大鼠唾液中的分布存在腺差。肾功能低下 ,导致了OFLX向Pr唾液中的移行性增大 ,但对M唾液的影响不明显。而OFLX向Pr唾液中分布的量与该唾液中药物浓度有关。     

Effect of mu and kappa opioid receptor agonists on rat plasma corticosterone levels

The effect of several mu and kappa opioid receptor agonists on rat plasma corticosterone levels, measured using radioimmunoassay, was investigated. The mu agonists, morphine and fentanyl, and the kappa agonists, U-50,488, tifluadom and bremazocine, all produced dose-related increases in rat plasma corticosterone levels. The effects of both fentanyl and U-50,488 were reversed by naloxone, indicating an action at opioid receptors. Pretreatment of the rats with the irreversible, mu-selective antagonist, beta-funaltrexamine, reduced the effect of fentanyl, but not that of U-50,488, indicating that both mu and kappa opioid receptors are involved in mediating this effect.