Effects of κ-Agonist on the Antinociception and Locomotor EnhancingAction Induced by Morphine in Mice

Takahashi, Toshiaki; Hasui, Kouichi; Aki, Yasuharu; Kimura, Shoji; Abe, Youichi

doi:10.1254/jjp.62.231

Cited by 33 publications

(16 citation statements)

References 47 publications

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“…In the kidney, NO has numerous important functions in the control of renal hemodynamics and excretory function (22,26,34). It is also well known that chronic blockade with the NOS inhibitor L-NAME results in hypertension and renal glomerular injury (3,37).…”

Section: Discussionmentioning

confidence: 99%

Dietary doses of nitrite restore circulating nitric oxide level and improve renal injury inl-NAME-induced hypertensive rats

Kanematsu

Yamaguchi²,

Ohnishi³

et al. 2008

American Journal of Physiology-Renal Physiology

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We have reported that pharmacological doses of oral nitrite increase circulating nitric oxide (NO) and exert hypotensive effects in N -nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. In this study, we examined the effect of a chronic dietary dose of nitrite on the hypertension and renal damage induced by chronic L-NAME administration in rats. The animals were administered tap water containing L-NAME (1 g/l) or L-NAME ϩ nitrite (low dose: 0.1 mg/l, medium dose: 1 mg/l, high dose: 10 mg/l) for 8 wk. We evaluated blood NO levels as hemoglobin-NO adducts (ironnitrosyl-hemoglobin), using an electron paramagnetic resonance method. Chronic administration of L-NAME for 8 wk induced hypertension and renal injury and reduced the blood iron-nitrosyl-hemoglobin level (control 38.8 Ϯ 8.9 vs. L-NAME 6.0 Ϯ 3.1 arbitrary units). Coadministration of a low dose of nitrite with L-NAME did not change the reduced iron-nitrosyl-hemoglobin signal and did not improve the L-NAMEinduced renal injury. The blood iron-nitrosyl-hemoglobin signals of the medium dose and high dose of nitrite were significantly higher than that of L-NAME alone. Chronic administration of a medium dose of nitrite attenuated L-NAME-induced renal histological changes and proteinuria. A high dose of nitrite also attenuated L-NAME-induced renal injury. These findings suggest that dietary doses of nitrite that protect the kidney are associated with significant increase in iron-nitrosyl-hemoglobin levels. We conclude that dietary nitrite-derived NO generation may serve as a backup system when the nitric oxide synthase/L-arginine-dependent NO generation system is compromised.vegetables; N -nitro-L-arginine methyl ester; kidney NITRIC OXIDE (NO) is a gaseous signaling molecule and exerts a variety of biological actions under physiological and pathophysiological conditions, such as regulation of the cardiovascular, inflammation, immune, and neuronal systems. NO also has numerous important functions in the kidney, such as the regulation of renal hemodynamics and glomerular microcirculation, the regulation of salt balance, the blunting of tubuloglomerular feedback, and the modulation of renal sympathetic nerve activity (18,26). Chronic blockade of nitric oxide synthases (NOSs) with N -nitro-L-arginine methyl ester (L-NAME) in rats results in severe hypertension and progressive kidney damage (3, 11). On the other hand, NO production seems to be low in chronic kidney disease (CKD) patients, and NO deficiency may play a role in CKD progression (5, 32). Treatment strategies to maintain the circulating NO level in healthy young people may be useful in preventing or slowing the progression of renal diseases.It is believed that NO is synthesized from L-arginine, NADPH, tetrahydrobiopterin, and the molecular oxygen catalyzed by NOSs in endothelial and other cells. The biological activity of NO is terminated by oxidation into nitrite and nitrate. Therefore, nitrite and nitrate in the blood are recognized as waste forms of NO. However, this dogma is now being challe...

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Section: Discussionmentioning

confidence: 99%

Dietary doses of nitrite restore circulating nitric oxide level and improve renal injury inl-NAME-induced hypertensive rats

Kanematsu

Yamaguchi²,

Ohnishi³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…However, interestingly, Toda et al (20,26) reported that Ang II caused relaxation in the helically cut strip of dog renal artery, and this relax ation was mediated by vasodilatory PGs. In fact, isolated AA has the ability to produce vasodilatory PGs (21) and NO (12). Then, we hypothesized that vasodilatory PGs and NO counteract the vasoconstrictor effect of Ang II on the isolated AA.…”

Section: Discussionmentioning

confidence: 97%

“…Ito et al (13) report ed that Ang II caused segmental constrictions and the strongest was observed in the segment close to the glo merulus using microperfused AA. While Ito et al isolated the AA with glomerulus, we isolated only the AA in our preparation (12), and both ends of the AA were cannulat ed with a pipette system (Figs. 1 and 3).…”

Section: Discussionmentioning

confidence: 99%

“…We used a method similar to that described previously to isolate and cannulate AA (12). Briefly, the kidney was exposed through a retroperitoneal flank incision, and the kidney was quickly removed and placed in iced modified Krebs Ringer solution.…”

Section: Methodsmentioning

confidence: 99%

“…These findings suggest that vasodilatory PGs modulate the vasoconstrictor effect of Ang II in the renal resistance vessels. Moreover, we reported that nitric oxide (NO) is synthesized and/or released in the rabbit AA under basal conditions and that this basal release of NO plays an im portant role in the basal tone of the AA (12). This effect of NO may modulate the action of Ang II on the AA.…”

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Effects of Angiotensin II on Isolated Rabbit Afferent Arterioles

Yoshida

Takahashi

Aki

et al. 1994

Japanese Journal of Pharmacology

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ABSTRACT-We examined the effects of angiotensin II (Ang II) on isolated rabbit afferent arterioles to assess the direct effect of Ang II at the resistance vessel level in the kidney. We microdissected the superficial afferent arteriole from the kidney of New Zealand White rabbits. The afferent arteriole was cannulated with a micropipette system, and the intraluminal pressure was set at 80 mmHg. Ang II did not change the lumen diameter of the afferent arterioles. After the afferent arterioles were pretreated with aspirin DL-lysine or indomethacin, Ang II (10-' M) caused transient vasoconstriction in the afferent arterioles. Ang II (10-' M) caused persistent constriction in the afferent arterioles pretreated with 1VG-nitro-L-arginine (10-4 M). Physiological doses of Ang II decresed the lumen diameter of the isolated afferent arterioles pretreated with A7'-nitro-L-arginine and aspirin DL-lysine. Dup753 (10-6 M), an AT1-receptor antagonist, abolished the vasoconstrictor effects of Ang II. These findings suggest that the isolated rabbit afferent arteriole has AT1 receptors, and the vasoconstrictor response of Ang II is counteracted by vasodilatory prostaglandins and nitric oxide.

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Role of efficacy as a determinant of locomotor activation by mu‐opioid receptor (MOR) ligands in female and male mice. II. Effects of novel MOR‐selective phenylmorphans with high‐to‐low MOR efficacy

Santos

Nassehi

Bow³

et al. 2023

Pharmacology Res & Perspec

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Low‐efficacy mu‐opioid receptor (MOR) agonists represent promising therapeutics, but existing compounds (e.g., buprenorphine, nalbuphine) span a limited range of low MOR efficacies and have poor MOR selectivity. Accordingly, new and selective low‐efficacy MOR agonists are of interest. A novel set of chiral C9‐substituted phenylmorphans has been reported to display improved MOR selectivity and a range of high‐to‐low MOR efficacies under other conditions; however, a full opioid receptor binding profile for these drugs has not been described. Additionally, studies in mice will be useful for preclinical characterization of these novel compounds, but the pharmacology of these drugs in mice has also not been examined. Accordingly, the present study characterized the binding selectivity and in vitro efficacy of these compounds using assays of opioid receptor binding and ligand‐stimulated [35S]GTPɣS binding. Additionally, locomotor effects were evaluated as a first step for in vivo behavioral assessment in mice. The high‐efficacy MOR agonist and clinically effective antidepressant tianeptine was included as a comparator. In binding studies, all phenylmorphans showed improved MOR selectivity relative to existing lower‐efficacy MOR agonists. In the ligand‐stimulated [35S]GTPɣS binding assay, seven phenylmorphans had graded levels of sub‐buprenorphine MOR efficacy. In locomotor studies, the compounds again showed graded efficacy with a rapid onset and ≥1 h duration of effects, evidence for MOR mediation, and minor sex differences. Tianeptine functioned as a high‐efficacy MOR agonist. Overall, these in vitro and in vivo studies support the characterization of these compounds as MOR‐selective ligands with graded MOR efficacy and utility for further behavioral studies in mice.

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Effects of κ-Agonist on the Antinociception and Locomotor EnhancingAction Induced by Morphine in Mice

Cited by 33 publications

References 47 publications

Dietary doses of nitrite restore circulating nitric oxide level and improve renal injury inl-NAME-induced hypertensive rats

Dietary doses of nitrite restore circulating nitric oxide level and improve renal injury inl-NAME-induced hypertensive rats

Effects of Angiotensin II on Isolated Rabbit Afferent Arterioles

Role of efficacy as a determinant of locomotor activation by mu‐opioid receptor (MOR) ligands in female and male mice. II. Effects of novel MOR‐selective phenylmorphans with high‐to‐low MOR efficacy

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