摘要:

Chronic administration of L-arginine (200 mg/kg i.p.) but not of D-arginine (200 mg/kg i.p.) twice a day for 4 days decreased the antinociceptive response to subcutaneously administered morphine-6-β-D-glucuronide (M6G), a potent metabolite of morphine, in male Swiss-Webster mice as measured by the tail-flick test. However, the antinociceptive response to intra-cerebroventricularly administered M6G was unaffected by chronic treatment with L-arginine. The decreased antinociceptive response to M6G (s.c.) was reversed by concurrent administration of NG-nitro-L-arginine (5 mg/kg i.p.), an inhibitor of nitric oxide synthase. Acute administration of L-arginine (200 mg/kg i.p.) had no effect on M6G-induced antinociception, but higher doses (400 and 800 mg/kg i.p.) decreased it. Since the antinociceptive response to centrally administered M6G was unaffected by chronic L-arginine treatment, the decreased antinociceptive response of peripherally administered M6G may be related to a decrease of M6G entry into brain structures responsible for antinociceptive action

ISSN:0031-7012    

DOI:10.1159/000139524

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The anti-inflammatory activity of 1-methylimidazole-2-thiol (methimazole), the most widely used antithyroid drug, was investigated. Methimazole had a marked inhibitory action on prostaglandin H synthase (IC50 = 10 µmol/l), inhibiting the peroxidase (IC50 = 330 µmol/l), although the cyclo-oxygenase was slightly activated. Methimazole was less potent than indometacin (IC50 = 1.7 µmol/l) on prostaglandin H synthase, but was more potent than acetylsalicylic acid (IC50 =160 µmol/l). Methimazole has been found to trap superoxide (O·2) radicals and to decrease the level of blood prostaglandin E2

ISSN:0031-7012    

DOI:10.1159/000139525

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The study was undertaken to characterize the effects of the porcine galanin [pGal(1–29)-NH2] analogue [Lys14]pGal(1–15)-NH2 on rat gastric fundus. [Lys14]pGal(1–15)-NH2 is a less potent contractile agent than pGal(1–29)-NH2 (EC50 74.1 vs. 43.7 nmol/l, respectively) and shows a significantly lower maximal response than pGal(1–29)-NH2. Concentration-contraction curves were constructed for pGal(1–29)-NH2 alone (control) and pGal(1–29)-NH2 in the presence of 10, 100, and 1,000 nmol/l of [Lys14]pGal(1–15)-NH2. [Lys14]pGal(1–15)-NH2 shifted the concentration-contraction curves of pGal(1–29)-NH2 significantly to the right, whereas their linear portions remained parallel to that for the pGal(1–29)-NH2 control. [Lys14]pGal(1–15)-NH2 markedly increased the EC50 of the respective pGal(1–29)-NH2 concentration-contraction curves. It did not substantially change the maximal response of the muscles to pGal(1–29)-NH2 and the form of the respective concentration-contraction curves. Schild’s plot gave a straight line with a slope of 0.84. The pA2 value for [Lys14]pGal(1–15)-NH2 was 8.23. [Lys14]pGal(1–15)-NH2 seems to be a partial Gal receptor agonist. Since the lack of specific Gal receptor antagonists in the gastrointestinal tract makes a precise characterization of its role as a motility modulator difficult, the position 14 in the pGal(1–29)-NH2 molecule looks as an attractive target in the search of a pure Gal receptor antagoni

ISSN:0031-7012    

DOI:10.1159/000139526

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

A new rabbit model of disused bladder was developed. Disused bladders were created by sagittal splitting of the bladders along the midline and closure of one side (reservoir side), leaving the remaining side unclosed (disused). The mucosa was dissected from some of the disused sides. Tissue elasticity and the weight of the detrusor muscle were decreased by bladder disuse. The responsiveness to field stimulation, bethanechol, ATP, KC1, or isoproterenol, was decreased by disuse. Tissue elasticity and responsiveness to stimuli were decreased to a lesser extent in disused tissue with intact mucosa. Results suggest that the bladder mucosa helps to preserve the function of the disused bladder.

ISSN:0031-7012    

DOI:10.1159/000139527

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The purpose of the present investigation was to examine the effects of KW-3902 [8-(noradamantan-3-yl)-1,3-dipropyl-xanthine], a selective and potent adenosine A1 receptor antagonist, in order to clarify the role of adenosine in the control of renal hemodynamics and urine formation in anesthetized dogs. KW-3902 was directly infused into the renal artery to eliminate the systemic effects of the drug. KW-3902 (10 µg/ kg/min) almost completely inhibited the renal vasoconstriction induced by adenosine via A1 receptors. Intrarenal infusion of KW-3902 did not affect mean arterial pressure, renal blood flow, creatinine clearance, or arterial plasma renin activity, but drastically increased urine flow, urinary excretion of sodium, and osmolar clearance. Inhibition of the renin-angiotensin system using CV-11974 [2-ethoxy-1-((2’-(1-H-tetrazole-5-yl)biphenyl-4-yl)methyl)-1-H-benzimidazole -7-carboxylic acid], a selective AT1 antagonist, did not affect the diuretic action of KW-3902. These data suggest that endogenous adenosine does not play a significant role in the control of renal hemodynamics in whole kidney, but that it plays an important role in preserving body fluid via the A1 receptor independent of the renin-angiotensin system in anesthetized do

ISSN:0031-7012    

DOI:10.1159/000139528

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Nitric oxide has been shown to decrease myocardial contractility and O2 consumption. This study was designed to evaluate the hypothesis that nitric oxide-mediated increases in cyclic GMP require elevated cyclic AMP to produce cardiac depression. Using isolated, Langendorff-perfused rat hearts, we determined the effects of intracoronary nitroprusside (NP, 1 and 10 mM) in the absence and presence of isoproterenol (ISO, 10–8 M) on cardiac function, O2 consumption, cyclic GMP and cyclic AMP. ISO, with and without NP, increased cyclic AMP (from 287 ± 21 to 477 ± 33 pmol/g) without altering cyclic GMP. Left-ventricular pressure increased from 97 ± 12 to 178 ± 9 mmHg and dP/dtmax from 1,786 ± 275 to 4,049 ± 354 mm Hg/s. NP increased cyclic GMP (from 4 to 30 pmol/g) in both the absence and presence of ISO, but NP did not alter cyclic AMP. Without ISO, NP insignificantly altered left-ventricular pressure; however, in the presence of ISO, NP significantly decreased left-ventricular pressure by –25 ± 4 mm Hg and decreased dP/dtmax by –619 ± 142 mm Hg/s. Isoproterenol increased O2 consumption, but the changes with NP were not significant. When this study was repeated in the presence of LY83583, a guanylate cyclase inhibitor, NP still produced cardiac depression in the presence of ISO. Therefore, cardiodepressant effects of NP were only observed against a background of inotropic stimulation with ISO. However, effects of NP on contractility were unrelated to increases in cyclic GMP or cyclic GMP-induced changes

ISSN:0031-7012    

DOI:10.1159/000139529

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

This study was designed to determine whether in isolated rabbit iris-ciliary bodies and monkey ciliary bodies, cGMP plays a role in the action of moxonidine, an α2- and imidazoline (Ii) receptor agonist. In field-stimulated rabbit iris-ciliary bodies, dose-related inhibition of norepinephrine release was induced by 8-Br-cGMP, moxonidine or sodium nitroprusside; 8-Br-cGMP in combination with moxonidine did not enhance inhibition of norepinephrine release. Sodium nitroprusside at intermediate and high concentrations stimulated cGMP production in rabbit iris-ciliary bodies, whereas moxonidine stimulated cGMP production modestly only at a high concentration. When iris-ciliary bodies were pretreated with a low concentration of moxonidine, sodium nitroprusside-stimulated cGMP production was enhanced from 1.6 to 2.2 pmol/mg protein. In field-stimulated monkey ciliary bodies, both sodium nitroprusside and moxonidine inhibited norepinephrine release. Pretreatment of electrically stimulated monkey ciliary bodies with sodium nitroprusside enhanced the suppressive effect of moxonidine on norepinephrine release. In monkey ciliary bodies, moxonidine raised cGMP production more than sodium nitroprusside did, but there was no synergism in cGMP production by combined treatment with moxonidine and sodium nitroprusside. These results suggest that cGMP could play a role in the ocular action(s) of moxonidine in ciliary bodies; however, involvement of cGMP in the action of moxonidine in monkey ciliary bodies seems to be more pronounced than in rabbit iris-ciliary bodies

ISSN:0031-7012    

DOI:10.1159/000139530

出版商:S. Karger AG    

年代:1997

数据来源: Karger