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

Yagmur Okcay, Cagil Onal Sis, Muhammed Cagri Ozpolat, Zeliha Rumanli,Kemal Gokhan Ulusoy,Oguzhan Yildiz,Ismail Mert Vural

FUNDAMENTAL & CLINICAL PHARMACOLOGY(2024)

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Abstract
BackgroundThe endocannabinoid system plays important roles in various systems, including the genitourinary system; however, its mechanism of action is not fully understood.ObjectivesThis study aimed to investigate the direct relaxant effects of anandamide and its possible mechanisms in isolated rat bladder and vas deferens tissues.MethodsTwenty-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 mu M 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.ResultsAnandamide 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.ConclusionsThe 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.
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Key words
anandamide,rat bladder,rat vas deferens,smooth muscle relaxation responses
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