The relaxation effect of endocannabinoid anandamide on isolated rat bladder and vas deferens tissues and possible mechanisms

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Yagmur Okcay, Cagil Onal Sis, Muhammed Cagri Ozpolat, Zeliha Rumanli, Kemal Gokhan Ulusoy, Oguzhan Yildiz, Ismail Mert Vural
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Abstract

Background

The endocannabinoid system plays important roles in various systems, including the genitourinary system; however, its mechanism of action is not fully understood.

Objectives

This study aimed to investigate the direct relaxant effects of anandamide and its possible mechanisms in isolated rat bladder and vas deferens tissues.

Methods

Twenty-one adult male Wistar albino rats were used. Bladder and vas deferens (prostatic and epididymal portions) tissues were mounted in 10 mL of organ baths. Relaxation responses to anandamide were recorded at 3 and 10 μM concentrations. After the rest period, the procedures were repeated in the presence of cannabinoid (CB) and vanilloid receptor antagonists, various potassium channel blockers, cyclo-oxygenase, and nitric oxide synthase inhibitors. In different tissues to investigate the Ca2+-channel antagonistic effect of anandamide, concentration–response curves to CaCl2 were obtained in the absence and presence of anandamide.

Results

Anandamide caused a significant relaxation response in the bladder and epididymal vas deferens tissues, but not in the prostatic portion. The effect of anandamide was antagonized in the presence of the CB1 antagonist AM251 or the non-selective potassium channel blocker tetraethylammonium in bladder tissue. In the epididymal vas deferens, anandamide significantly inhibited the calcium contraction responses, especially at high concentrations. The CB2 antagonist AM630 reversed this inhibition.

Conclusions

The results show that anandamide has a direct relaxant effect on the isolated rat bladder and epididymal vas deferens. Anandamide triggers different mechanisms in different types of tissues, and further studies are needed to elucidate the mechanism of action of anandamide.

内源性大麻酰胺对离体大鼠膀胱和输精管组织的松弛作用及其可能机制。
背景:内源性大麻素系统在包括泌尿生殖系统在内的多个系统中发挥着重要作用,但其作用机制尚未完全明了:本研究旨在探讨安乃近在离体大鼠膀胱和输精管组织中的直接松弛作用及其可能机制:方法:使用 21 只成年雄性 Wistar 白化大鼠。将膀胱和输精管(前列腺和附睾部分)组织装入 10 mL 的器官浴中。记录 3 μM 和 10 μM 浓度的安乃近松弛反应。休息一段时间后,在大麻素(CB)和香草素受体拮抗剂、各种钾通道阻滞剂、环氧化酶和一氧化氮合酶抑制剂的作用下重复上述过程。为了研究安乃近对 Ca2+ 通道的拮抗作用,研究人员在不同组织中,在没有安乃近和有安乃近的情况下,测定了 CaCl2 的浓度-反应曲线:结果:在膀胱和附睾输精管组织中,安乃近酰胺引起了明显的松弛反应,但在前列腺部分却没有。在膀胱组织中,如果有 CB1 拮抗剂 AM251 或非选择性钾通道阻断剂四乙基铵,安乃近的作用就会被拮抗。在附睾输精管中,安乃近能显著抑制钙离子收缩反应,尤其是在高浓度时。CB2 拮抗剂 AM630 逆转了这种抑制作用:结果表明,安乃近对离体大鼠膀胱和附睾输精管有直接的松弛作用。安乃近在不同类型的组织中触发了不同的机制,需要进一步的研究来阐明安乃近的作用机制。
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来源期刊
CiteScore
5.30
自引率
6.90%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.
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