Which molecular targets do we need to focus on to improve lower urinary tract dysfunction? ICI‐RS 2017

Abstract

New molecular targets for drugs aiming at improvement of voiding function can be identified, but their translational impact remains to be established.

Inhibition of Female and Male Human Detrusor Smooth Muscle Contraction by the Rac Inhibitors EHT1864 and NSC23766

“…Similarly, the involved neurotransmitters accounting for EFS-induced contractions in our tisses were not identified. Neurogenic contractions of detrusor tissues are assumed to be largely or solely cholinergic under normal conditions, while purinergic contractions may contribute to detrusor smooth muscle tone under pathologic conditions, including DO and OAB (Saito et al, 1993;Palea et al, 1995;D'Agostino et al, 2000;Elliott et al, 2013;Andersson, 2015;Kushida and Fry, 2015;Andersson et al, 2018). The identity of neurotransmitters, a possible purinergic contribution to smooth muscle tone, and the pathological background have not been addressed in our tissues.…”

Prostaglandin E2 and F2alpha Modulate Urinary Bladder Urothelium, Lamina Propria and Detrusor Contractility via the FP Receptor

“…The U&LP not only provides a physical barrier between urine and the bladder wall but is also capable of releasing chemicals like acetylcholine which can influence the contractility of the detrusor ( Moro et al, 2011 ). Furthermore, it is also capable of responding to external signals like noradrenaline ( Moro et al, 2013 ), nitric oxide ( Moro et al, 2012 ), the five primary prostaglandins ( Stromberga et al, 2020b ), and histamine ( Stromberga et al, 2019 , 2020a ), as well as release ATP ( Andersson et al, 2018 ). It is known that cells found in U&LP can express both EP1 and EP2 receptors ( Rahnama’i et al, 2010 ) indicating that they are capable of responding to PGE 2 and eliciting a contractile response.…”

International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin E2Receptors (EP1–4) and Prostacyclin Receptor (IP): Specific Roles in Pathophysiologic Conditions

“…Prostanoids participate in controlling the relaxation and contraction of urinary bladder and urethra, thus affecting voiding and micturition, respectively ( Andersson et al, 2018 ). They also play an important role in various parts of the kidney and ureters, thus controlling salt and water retention as well as renin secretion in human and experimental animals ( Grantham and Orloff, 1968 ; Sonnenburg and Smith, 1988 ; Hao and Breyer, 2008 ).…”