PERSISTENT DESENSITIZATION OF THE BETA(2) ADRENOCEPTORS EXPRESSED BY CULTURED EQUINE SWEAT GLAND EPITHELIAL-CELLS

Adrenaline, forskolin and ATP all evoked accumulation of cyclic AMP in equine sweat gland epithelial cells, although the response to adrenal ine was more transient than that to forskolin and ATP. Cells preincuba ted in (10 mu mol l(-1), 32 min) showed essentially homologous desensi tisation, and this phenomenon reversed slowly (half-time 6.3+/-0.9 h), After 10 min of recovery from preincubation in adrenaline, isobutylme thylxanthine (IBMX, 5 mmol l(-1)) had no effect upon the desensitisati on and the cells showed no loss of sensitivity to ATP and forskolin. A fter 10 h, however, the persistent desensitisation was partially rever sed by IBMX and the cells showed reduced responses to ATP and forskoli n, Increased phosphodiesterase activity may thus contribute to the per sistent desensitisation. Experiments using forskolin-preincubated (100 mu mol l(-1), 32 min) cells suggested that increased cytosolic cyclic AMP levels did not underlie the initial loss of sensitivity to adrena line but that this second messenger may initiate the series of events leading to the generalised loss of sensitivity seen after 10 h.