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

Abstract

In the rabbit bladder, pregnancy has been shown to induce a significant decrease in both muscarinic receptor density and response to muscarinic stimulation. Neonatal rabbit bladders have a high muscarinic receptor density and contractile response to bethanechol stimulation. The bladders from 7 gravid rabbits, 7 age-matched virgin controls, and 32 fetal rabbits of 3 week gestation were studied. Compared to control tissue, filtration binding demonstrated receptor density to be 24.3% lower in gravid bladder dome, 41.2% lower in gravid bladder base, and 114.8% higher in fetal bladders. While total receptor density was not different from control in gravid heart, fetal hearts showed a 2.5 fold increased receptor density. There was also a 61% reduction in muscarinic receptor density in the gravid uterus.Immunoprecipitation assays using muscarinic receptor subtype specific antisera were used to measure the relative levels of m1, m2, m3 and m4 receptors. The m2 receptor was the predominant subtype in the bladder and uterus, and the only subtype detected in rabbit heart. The m3 receptor protein was also present, but in lower levels in the bladder and uterus. The m1 and m4 receptors were not detected in any of the tissues studied. Furthermore, the relative percent of each receptor did not statistically change for the gravid or fetal rabbit bladder, uterus, or heart, when compared to its control. Differences in the contractile response to cholinergic stimulation of the gravid bladder and uterus, and of the fetal bladder then, can be attributed to changes in muscarinic receptor density and not to changes in receptor subtype.

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

“…These studies revealed a high muscarinic receptor density at birth; no significant changes in the cholinergic innervation over the first 6 weeks of postnatal development in the rabbit [17] but a decrease in potency and efficacy of carbachol and ATP during the first month of newborn rats [32]. So far, only one study has evaluated that muscarinic receptor subtypes are expressed to a significantly greater extent in fetal bladders [5]. In this study, we have studied muscarinic M 2 and M 3 receptor expression and function in juvenile and adult porcine detrusor to compare detrusor contractile function in premature and mature organisms.…”

Increased maternal intraabdominal pressure alters the contractile properties of fetal rabbit bladder

“…The pressure in the bladder and the pressure generated by the gravid uterus during the last trimester may also affect the IAMNP and the fetal bladder. The pregnancy causes a decrease in muscarinic receptor density in both the rabbit bladder dome and the base by 24% to 41% [21], which explains previous observation of decreased contractile response to bethanechol [23]. It has been also reported that increased IAP causes cholinergic hyposensitivity in the adult rabbit bladders [6].…”

“…Muscarinic receptors of M3 subtype are also present, but with lower density. M1 and M4 are not found in the fetal and neonatal rabbit bladders [21].…”

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

“…In fetal rabbit bladder an increased density of both M 2 and M 3 (protein) has been reported, with no change in the M 2 /M 3 ratio. 20 Such increased receptor density might be involved in the increased response to the nonselective muscarinic agonist bethanechol in fetal rabbit bladder, 6 and might then also play a role in the increased response to muscarinic agonists in the present experiments. Using quantitative PCR we found that the expression levels of both M 2 and M 3 mRNA were highly increased in neonatal bladder (D0/D7) compared to adult, reaching highest significance at D7, and with a similar M 2 /M 3 ratio throughout ages (AE10, compared to AE9 at the protein level 21 ).…”