Proceedings of the Physiological Society, 19‐20 May 1989, Leeds Meeting: Communications

Abstract

XVe have previously reported to the Society the localization of fl-adrenoceptor subtypes in rat urinary bladder (Morrison et al. 1986). Using quantitative lightmicroscopic autoradiographv. changes in the density and distribution of f,-adrenoceptors in the bladder following both afferent and autonomic denervation were studied.Bladders were obtained from female XVistar rats (250-300 g) Afferent denervated bladders were obtained from rats treated neonatally with capsaicin. Unilateral and bilateral surgically denervated bladders were taken 14 days after nerve transection (halothane anaesthesia). Studies were performed on three animals from each group.The tissue was snap-frozen in Arcton 12 cooled to -196 'C. Tissue sections, 20 ,am thick, were cut on a cryostat and thaw-mounted onto poly-1-lysine coated slides. The tissue sections were incubated with [I251]iodocyanopindolol for 2 h at 37 'C. The distribution of the/,1-and f82-adrenoceptor subtypes were respectively determined by incubating with radioligand in the presence of either 10' m ICI 118,551 (a selective fl2-antagonist) or 10-7 m betaxolol (a selective /11-antagonist). Non-specific binding accounted for less than 5 % of total. Autoradiograms were generated as described by Carstairs et al. (1985). Autoradiographic grain density over sections of bladder dome was quantified using a Lietz MPV densitometer; quantification was performed on 35 sections from each bladder.In bladders from control animals ,-adrenoceptors were present over both the smooth muscle and epithelium, the /12-subtype accounting for 80% of the smooth muscle and 90 % of the epithelial adrenoceptors. Neonatal capsaicin treatment resulted in bladder hypertrophy, however there was no change in the densities of either /l3-or /12-adrenoceptors in the bladder. Unilateral denervation produced no hypertrophy, but there was a 2-6-fold increase in ,%-receptor density in the smooth muscle. Following bilateral denervation, hypertrophy was marked and resulted in an approximate 3-fold increase in the sectional area of smooth muscle on each slide. The density of /1-adrenoceptors per unit area was unchanged relative to controls, but 82-adrenoceptor density increased by 25 %. Epithelial /ll-adrenoceptor density increased 2 2-fold following unilateral denervation and 6 3-fold following bilateral denervation. Changes resulting from unilateral denervation were not restricted to the side of the lesion. It is proposed that changes in /I-adrenoceptor density following denervation reflect an upregulation of receptor number following loss of endogenous catecholamine.\N'ork supported bY the WN'ellcome Trust.