Abstract
Current pharmacological treatment options for many bladder contractile dysfunctions are not suitable for all patients, thereby bringing interest to the investigation of therapies that target a combination of receptors. This study aimed to compare responses of PGE2 on the urinary bladder urothelium with lamina propria (U&LP, also called the bladder mucosa) or detrusor smooth muscle and attempt to identify the receptor subtypes mediating PGE2 contractile responses in these tissues. In the presence of selective EP1 – 4 receptor antagonists, varying concentrations of PGE2 were applied to isolated strips of porcine U&LP and detrusor that were mounted in organ baths filled with Krebs-bicarbonate solution and gassed with carbogen. The addition of PGE2 (1 and 10 μM) and PGF2α (10 μM) to U&LP preparations caused significant increases in the baseline tension and in the spontaneous phasic contractile frequency. In detrusor preparations, significant increases in the baseline tension were observed in response to PGE2 (1 and 10 μM) and PGFα (10 μM), and spontaneous phasic contractions were initiated in 83% of preparations. None of the selective PGE2 receptor antagonists inhibited the increases in baseline tension in both U&LP and detrusor. However, the antagonism of PGF2α receptor showed significantly inhibited contractile responses in both layers of the bladder. This study presents prostaglandin receptor systems as a potential regulator of urinary bladder contractility. The main contractile effects of PGE2 in both U&LP and detrusor are mediated via the FP receptor with no observed contribution from any of the four EP receptors.
Highlights
Bladder contractile dysfunctions, such as overactive bladder (OAB) and underactive bladder (UAB), are common lower urinary tract dysfunctions that lower the overall quality of life in people living with it (Haylen et al, 2010; D’ancona et al, 2019), heightens the likelihood of developing depression and anxiety, as well as increase healthcare usage (Milsom et al, 2012)
Bladder contractions are under the control of the parasympathetic nervous system (De Groat et al, 1981) and mediated by the release of acetylcholine that acts upon the M2 and M3 muscarinic receptors found in the detrusor smooth muscle (Hegde et al, 1997; Sigala et al, 2002)
This study presents prostaglandin E2 as a potential contributor to the overall urinary bladder contractility and showcases the ability of isolated urothelium with lamina propria to respond to this inflammatory mediator
Summary
Bladder contractile dysfunctions, such as overactive bladder (OAB) and underactive bladder (UAB), are common lower urinary tract dysfunctions that lower the overall quality of life in people living with it (Haylen et al, 2010; D’ancona et al, 2019), heightens the likelihood of developing depression and anxiety, as well as increase healthcare usage (Milsom et al, 2012). It has been recognized that the urothelium, which lines the lumen of the bladder, is capable of responding to mechanical, chemical and thermal stimuli (Birder, 2006; Stromberga et al, 2019, 2020b). It is capable of releasing several signaling molecules in response to stretch, including acetylcholine (Moro et al, 2011) ATP and nitric oxide (Ferguson et al, 1997; Fry and Vahabi, 2016) that are involved in the modulation of the micturition reflex. The involvement of the urothelium and the underlying lamina propria should be considered as potential contributors to bladder contractile pathology
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