Effects of Pregnancy on Muscarinic Receptor Density and Function in the Rabbit Urinary Bladder

Abstract

The contractile response of the rabbit urinary bladder to field stimulation consists of both cholinergic and purinergic components. In general, approximately 60% of the contractile response to field stimulation is cholinergic and 40% is purinergic. Although the purinergic response represents a significant proportion of the initial (phasic) pressure response to field stimulation of the isolated whole bladder, it contributes only 10–15 % of the ability of field stimulation to empty the bladder. The current study investigates the effects of pregnancy on the contractile responses of the isolated urinary bladder to cholinergic and purinergic stimulation. The results of these studies indicate that pregnancy induces substantial changes in the physiology and pharmacology of the urinary bladder. The following data are consistent with the theory that pregnancy substantially increases the relative purinergic component of the response to field stimulation (and presumably neuronal stimulation): (1) there was a significantly greater response of the bladders isolated from pregnant rabbits to low-frequency field stimulation; (2) atropine was more effective at inhibiting the pressure generation of bladders isolated from virgin female rabbits; (3) field stimulation was more effective at emptying bladders isolated from virgin female rabbits; (4) the response of the bladders from pregnant rabbits to bethanechol was significantly reduced, whereas the response to ATP was significantly increased. In addition to these effects of pregnancy on bladder physiology, pregnancy induced a 50% decrease in the muscarinic receptor density of the urinary bladder body, which correlated very well with the 50% decrease in the contractile response to bethanechol.

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

“…Despite no significant change in gravid bladder weight or in-vitro bladder capacity, pregnancy induced a 35% decrease in muscarinic receptor density, based on radioligand binding (34 fMol/mg vs 22), a 50% reduction in response to bethanechol, and a markedly increased response to ATP (16). Our data closely mirrors and reconfirms that pregnancy induces muscarinic receptor down regulation in the bladder, as well as in the uterus.…”

“…In the pregnant human the bladder undergoes many functional changes, among them an increase in residual volume, decrease in bladder tone and increase in urinary stress incontinence. The decreases in muscarinic receptor density in both the rabbit bladder dome and base by 24% to 41%, and the previously detailed decreases in gravid bladder contractile response to bethanechol (16), help to explain these clinical findings.…”

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

“…Receptor binding studies in bladder tissue from pregnant animals revealed a significantly reduced muscarinic receptor density (50%), corresponding to the decrease in response to bethanechol of the whole bladder. The results were interpreted to mean that pregnancy induced an increase in the purinergic and a decrease in the cholinergic components of the urinary bladder response to field stimulation (Levin et al, 1991). A reduction of the muscarinic receptor density in the pregnant rabbit bladder was confirmed by other investigators (Baselli et al, 1999).…”

“…Thus, in the presence of bethanechol, bladder strips from pregnant rabbits generated 50% less tension in response to calcium than those from nonpregnant rabbits (Zderic et al, 1990). The isolated whole bladder from pregnant animals responded to low-frequency stimulation and to ATP with a greater increase in intravesical pressure than did preparations from virgin rabbits, whereas the response to bethanechol was greater in the virgin rabbits (Levin et al, 1991). Receptor binding studies in bladder tissue from pregnant animals revealed a significantly reduced muscarinic receptor density (50%), corresponding to the decrease in response to bethanechol of the whole bladder.…”

Effect of Thyroxine on Urinary Bladder Autonomic Receptor Densities and Contractility

“…Estrogen administra tion has been shown to result in marked increases in a-adrenergic and muscarinic re ceptors [7], Pregnancy induces a significant decrease in the contractile response to musca rinic stimulation which has been correlated with a decrease in muscarinic receptors [8], In view of the marked effects of estrogen (and pregnancy) on autonomic receptor density, and the contractile response to autonomic agonists, it was appropriate to determine the actions of thyroid hormone on the response of the bladder to autonomic stimulation, and the density of autonomic receptors.…”