Developmental Factors in the Contractile Response of the Rabbit Bladder to Both Autonomic and Non-Autonomic Agents

Abstract

Previous work in this laboratory has demonstrated that the bladders of 1-day-old and 1-week-old rabbits generate higher pressures in whole-bladder preparations than bladders from mature 8-week-old rabbits. In addition, the density of cholinergic receptors does not change during this maturation period. The present study was designed to determine if the increased responsiveness of the neonatal bladder was specific for cholinergic stimulation. Using bladder strips, we have demonstrated that the newborn bladders generated much greater tension in response to ATP, serotonin, histamine, and substance P. The response of the 1-day-old bladder smooth muscle to these contractile agents was at least double the response of the 8-week-old bladders. However, the response of all age groups to bethanechol was approximately the same, and the response to KC1 was only 40% greater in the 1-day-old bladders as compared to the adult. These current studies indicate that the newborn bladder responds to a variety of nonadrenergic, noncholinergic agonists to a significantly higher degree than the adult bladder, and that maturation is accompanied by substantial changes in the pharmacology of the bladder.

Muscarinic Receptor Subtypes in Normal, Fetal, and Gravid Rabbit Bladder, Heart and Uterus

“…This has been confirmed by others, where muscarinic receptor density, response to cholinergic agonists, and bladder cholinergic innervation are present at high levels at birth (4 weeks gestation) and remain stable with increasing age, up to 15 weeks of life (18). In addition, neonatal bladder responses to ATP, serotonin, histamine and substance P were found to be 2.5 to 4.8 fold greater than in adult bladders (2). Nonadrenergic, noncholinergic neurotransmitters appear to play a greater role than once thought in the control of fetal and neonatal bladder function.…”

“…Neonatal rabbit bladders show a marked, yet stable muscarinic receptor density and contractile response to bethanechol and field stimulation (2). To understand the mechanism of these changes in muscarinic response, we studied the muscarinic receptor subtypes and receptor densities in the gravid, virgin, and fetal rabbit bladder.…”

Urinary bladder function in conscious rat pups: a developmental study

“…By the end of this period, the sacral/perigenital bladder reflex that prevails during ontogeny is downregulated, and a mature supraspinal micturition reflex is established/activated, allowing voluntary/ spontaneous voiding (10,21,29). The exact determinants of the continued development are not known; however, increasing contribution of various neurotransmitters, changes in the sensitivity of urinary bladder smooth muscle contractility to stimulation, and functional maturation of synaptic transmission and higher brain centers have been shown to play a role (1,8,22,27,37). In addition to changes in bladder function, modulation of myogenic activity and progressive changes in urodynamic parameters have been described (23,24,33,34).…”

Maturation of stretch‐induced contractile activity and its muscarinic regulation in isolated whole bladder strips from rat

“…6,7 The presented new data include the observation of a strong response to the muscarinic component ABET (which has moderate M 2 -selectivity) in D0/D7 rat bladders (which is absent in adult bladder), which provides some evidence for an enhanced function of M 2 -receptors. Furthermore the amount of both M 2 and M 3 mRNA is significantly increased in D0/D7 bladders, with the highest values found at D7.…”

“…Stretch-induced contractile activity (SIC) in bladder strips 4,5 has been reported to undergo an evolution from high-amplitude low-frequency contractions in the neonatal period to low-amplitude highfrequency contractions in adults. Pharmacologically the responses to KCl, 6,7 Carbachol (CA), 7 ATP, 6,7 and Substance P 6 were significantly increased in neonatal bladders from different species. Further reports have been made on age-dependent evolutions in endothelin receptors, 8 neuropeptide Y-and CGRP-related immunoreactive nerve fibres, 9 purinoreceptor expression 10 and calcium-handling in excitation-contraction coupling.…”