Oestrogen-induced changes in muscarinic receptor density and contractile responses in the female rabbit urinary...

Mature ovariectomized rabbits were treated for 1, 4 or 8 weeks with oestrogen, and the effects on contractile responses and on muscarinic receptor density in the isolated urinary bladder were studied. Oestrogen treatment caused a significant increase in the weight of the bladders. The responses to K+ (124 mM) were depressed, but not the maximum responses to carbachol. The frequency-response curve to electrical stimulation was shifted to the right after 4 and 8 weeks of treatment, but the maximum response was not reduced. There was also a (non-significant) shift to the right of the carbachol concentration-response curve. Pre-treatment with scopolamine revealed a significant reduction of the non-cholinergic response to electrical stimulation after oestrogen treatment compared to controls. Binding of [3H]quinuclidinyl benzilate (QNB) was saturable and of high affinity. There were no changes in apparent dissociation constant after oestrogen treatment. However, the muscarinic receptor density decreased already after 1 week of treatment and was only 10% of the control after 4 weeks. It is concluded that oestrogen treatment causes a down-regulation of muscarinic receptors in the rabbit urinary bladder, but the consequences for contractile activation through muscarinic receptors seem to be small.