Developmental regulation of nerve and receptor mediated contractions of mammalian urinary bladder smooth muscle

The development of nerve-induced activation, receptor properties and cellular signalling was examined by comparing the urinary bladder of new-born (0-2 days) and adult mice. Tissue strips were isolated and the effects of different neuromuscular agents on force were investigated during electrical field stimulation. The nerve-induced contractions of the urinary bladders from new-born mice were less influenced by desensitisation with alpha, beta-methylene ATP and more sensitive to scopolamine compared with those of the adult bladder. There were no differences in alpha, beta-methylene ATP or ATP responsiveness between adult and new-bom tissue, showing that the lower purinergic component of the nerve-induced responses in the new-bom mice was clue to properties of the transmitter release rather than to a change in receptor function. Dose-response curves for carbachol revealed a lower peak response in new-bom bladders compared with adults. The phasic component of the cholinergic contractions was pronounced and initiated at low carbachol concentrations in the new-born tissue. The carbachol contractions of both new-bom and adult urinary bladder tissue were inhibited by the Rho kinase inhibitor Y27632 and by the protein kinase G activator 8-Br-cGMP. However, the sustained phase of carbachol contraction was significantly less sensitive to Y27632 and 8-Br-cGMP in new-bom tissue. These results suggest that the receptor mediated calcium sensitisation mechanism is less prominent in new-born compared with adult mice and that the contractions of new-born bladders are less influenced by the nitric oxide (NO)-cGMP inhibitory pathway. (c) 2006 Elsevier B.V. All rights reserved.