Abstract
The aim of the research was to assess the impact of O-1602—novel GPR55 and GPR18 agonist—in the rat model of detrusor overactivity (DO). Additionally, its effect on the level of specific biomarkers was examined. To stimulate DO, 0.75% retinyl acetate (RA) was administered to female rats’ bladders. O-1602, at a single dose of 0.25 mg/kg, was injected intra-arterially during conscious cystometry. Furthermore, heart rate, blood pressure, and urine production were monitored for 24 h, and the impact of O-1602 on the levels of specific biomarkers was evaluated. An exposure of the urothelium to RA changed cystometric parameters and enhanced the biomarker levels. O-1602 did not affect any of the examined cystometric parameters or levels of biomarkers in control rats. However, the O-1602 injection into animals with RA-induced DO ameliorated the symptoms of DO and caused a reversal in the described changes in the concentration of CGRP, OCT3, BDNF, and NGF to the levels observed in the control, while the values of ERK1/2 and VAChT were significantly lowered compared with the RA-induced DO group, but were still statistically higher than in the control. O-1602 can improve DO, and may serve as a promising novel substance for the pharmacotherapy of bladder diseases.
Highlights
According to the International Continence Society definition, overactive bladder (OAB) is a chronic ailment with urinary urgency, and usually presents with enhanced daytime frequency and nocturia as the main symptoms
The objective of the current research was to evaluate the effects of O-1602, an atypical synthetic cannabinoid which acts as a potent agonist of the GPR55receptor and biased agonist of the GPR18 receptor [61,62], on urodynamic parameters in the animal model of detrusor overactivity (DO) induced with the transient intravesical infusion of retinyl acetate (RA), in conscious female rats during cystometry
The aim of the study was to assess in vivo the effect of O-1602 on the micturition cycle of conscious animals, female rats, in the animal model of DO [63] previously developed by the research team, and its applicability in DO/OAB therapy
Summary
According to the International Continence Society definition, overactive bladder (OAB) is a chronic ailment with urinary urgency, and usually presents with enhanced daytime frequency and nocturia as the main symptoms. OAB, one of the most prevalent lower urinary tract (LUT) conditions, is diagnosed as often in females as in males (in total approximately 10–17% of the population over 18 years of age) [5,6,7], but gender-dependent differences in manifestations, mainly caused by anatomical and physiological dissimilarities in the lower part of the urinary tract, are observed [8,9,10,11]. OAB has a great influence on the quality of life of millions of people worldwide. It is well established that OAB symptoms significantly lower the quality of life, mainly via its impact on everyday activities [3].
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