Muscarinic receptor expression and receptor-mediated detrusor contraction: comparison of juvenile and adult porcine tissue

Abstract

Urinary bladder function is known to mature during fetal and postnatal development, including changes in neurotransmitter regulation of detrusor contraction. However, only few experimental data are available about muscarinic receptor antagonist function in the urinary bladder from young animals. In the present study, we compare the muscarinic receptor-mediated contractions in juvenile and adult porcine detrusor and the effects of antimuscarinic compounds. Urinary bladders from young (8-12 weeks; 12- to 35-kg body weight) and mature pigs (>40 weeks; >100 kg) were compared. Muscarinic receptor expression was assessed by real time polymerase chain reaction and radioligand binding. Muscle contraction was measured with a force transducer; L-type Ca2+ currents (ICa,L) of isolated detrusor myocytes were recorded with standard voltage clamp technique. Juvenile and adult detrusor expressed similar quantities of the messenger RNA of M2 and M3 receptors. The number of [3H]QNB-binding sites and their affinity for the radioligand were also similar between juvenile and adult detrusor. In contrast, maximum contractile responses to the muscarinic receptor agonist carbachol were slightly larger in juvenile than adult bladders. On the other hand, carbachol was slightly less potent in juvenile than in adult tissue. The M3 antagonist DAU 5884 and the spasmolytic drug propiverine inhibited contractile responses with comparable efficacies and potencies in juvenile and adult tissue. ICa,L was somewhat smaller in juvenile than in adult cells. Taken together, these data suggest that expression and function of M2 and M3 receptors are similar in the detrusor of juvenile and mature pigs. Therefore, similar responses to antimuscarinic compounds could be expected in young and adult patients.

Age‐dependent decrease in TRPM4 channel expression but not trafficking alters urinary bladder smooth muscle contractility

“…Additionally, 10 µM α,β‐methylene ATP, a purinergic agonist, elicited significantly greater Ca 2+ transient currents in adult UBSM myocytes compared to their fetal counterpart suggesting greater P2X receptor expression in the adult (Wu et al, 2006). In line with previously mentioned studies, adult porcine UBSM (>40 weeks), when compared to juvenile UBSM (8–12 weeks), showed a higher number of muscarinic receptor binding sites as well as an increased potency to carbachol for stimulation of contractility (Wuest et al, 2008). In another study, investigators determined via PCR that there was a lower expression of purinergic receptors in human fetal bladder compared to adults (O'Reilly et al, 2001).…”

What can maturations studies teach us about adult detrusor overactivity?

“…2 At least in pigs the relative contribution of cholinergic mechanisms to bladder contraction appears to increase from juvenile towards adult animals. 3 While the expression of muscarinic receptors does not markedly change in such pigs, 4 fetal rabbits 5 and newborn rats 2 exhibit enhanced muscarinic receptor expression. On the other hand, juvenile rats also were reported to have greater b-adrenoceptor expression.…”