Alterations in histamine responses between juvenile and adult urinary bladder urothelium, lamina propria and detrusor tissues

Abstract

Russ chess-Williams & christian Moro * Inflammatory mediators may have a role in various lower urinary tract disorders. Histamine is known to induce significant increases in both the tension and frequency of spontaneous phasic contractions in both urothelium with lamina propria (U&LP) and detrusor muscle via the activation of H1 receptor in juvenile animal models. However, it is unclear whether age affects these contractile responses to histamine. This study assessed the histamine receptor subtypes mediating contraction in juvenile and adult porcine bladders and compared the urothelium with lamina propria and detrusor responses to histamine. Isolated tissue bath studies were conducted using strips of porcine U&LP and detrusor obtained from juvenile (6 months) and adult (3 years) animals exposed to histamine receptor agonists and antagonists. Treatment with histamine (100 µM) in U&LP of juvenile animals caused increases in baseline tension by 47.84 ± 6.52 mN/g (p < 0.001, n = 51) and by 50.76 ± 4.10 mN/g (p < 0.001, n = 55) in adult animals. Furthermore, the frequency of spontaneous phasic contractions was significantly enhanced in response to histamine in U&LP of both juvenile and adult tissues (p < 0.001 for both age groups). Treatment with an H2 agonist in U&LP of juvenile animals decreased baseline tension by 13.97 ± 3.45 mN/g (n = 12, p < 0.05), but had no effect in adult animals. Inhibition of H1 receptors resulted in significantly reduced contractile responses of U&LP and detrusor to histamine in both juvenile and adult animals (p < 0.05). Treatment with an H2 receptor antagonist significantly enhanced contractions in juvenile preparations (n = 10, p < 0.05) but had no effect in adult preparations (n = 8). In detrusor, treatment with histamine (100 µM) in juvenile tissues showed a significantly higher increase in baseline tension of 19.10 ± 4.92 mN/g (n = 51) when compared to adult tissues exhibiting increases of 8.21 ± 0.89 mN/g (n = 56, p < 0.05). The increases in the baseline tension were significantly inhibited by the presence of H1 receptor antagonists in both juvenile and adult detrusor preparations. Treatment with either the H2 receptor antagonist or agonist in detrusor had no effect on both juvenile and adult tissues. Therefore, the histamine receptor system may play an essential role in the maintenance of bladder function or in bladder dysfunction observed in some lower urinary tract disorders. Normal bladder function deteriorates throughout adult life, age appearing to have a direct effect on bladder sensation, contractility and the ability to postpone voiding 1. Ageing is associated with several changes that occur in the urinary bladder, such as a reduction in bladder capacity 2 and an increase in bladder sensitisation 3. It is also linked with marked increases in the prevalence of lower urinary tract symptoms, such as urinary frequency, voiding difficulties, decreased bladder contractions (as seen in underactive bladder) or uninhibited bladder contractions (as seen in overactive bladder) 1. Urin...

The Dependence of Urinary Bladder Responses on Extracellular Calcium Varies Between Muscarinic, Histamine, 5-HT (Serotonin), Neurokinin, Prostaglandin, and Angiotensin Receptor Activation

“…A paired t -test was used to analyse tissue responses before and after the addition of agonist. A paired Student’s two-tailed t -test was used to analyse the significance of results when comparing tissues with direct controls, as per previous studies ( Stromberga et al, 2020a ). A one-way ANOVA with Tukey post-test was also undertaken to compare the means where more than two variables were assessed.…”

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.…”

“…Prostaglandin E 2 , in particular, is thought to be the most likely contributor to bladder disorders as it can modulate bladder function via afferent signaling ( Andersson, 2010 ) and potentially detrusor overactivity by sensitizing capsaicin-sensitive afferent nerve endings ( Maggi, 1988 ; Park et al, 1999 ). It is released upon degranulation of mast cells ( Schmauder-Chock and Chock, 1989 ) together with histamine, which is also capable of impacting the bladder contractility ( Stromberga et al, 2019 , 2020a ). Moreover, PGE 2 is produced locally in the bladder in response to distension and inflammation ( Funk, 2001 ).…”

The five primary prostaglandins stimulate contractions and phasic activity of the urinary bladder urothelium, lamina propria and detrusor

“…As no animals were bred, harmed, culled, interfered, or interacted with as part of this research project, Animal Ethics Approval was not required for offal use [17]. Urothelium with lamina propria was dissected from the underlying detrusor layer, consistent with methods carried out in past studies [18][19][20][21], and cut in strips. Adjacent strips of U&LP and detrusor (10 mm × 5 mm) were tied vertically between an isometric force transducer (MCT050/D, ADInstruments, Castle Hill, Australia) and a fixed hook in 10 mL organ baths (Labglass, Brisbane, Australia), and superfused with Krebs-bicarbonate solution (NaCl 118.4 mM, NaHCO 3 24.9 mM, CaCl 2 1.9 mM, MgSO 4 2.41 mM, KCl 4.6 mM, KH 2 PO 4 1.18 mM and D-glucose 11.7 mM) and carbogen gas (95% oxygen and 5% carbon dioxide) at 37°C.…”