Persistent desensitisation of the β2 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 adrenaline was more transient than that to forskolin and ATP. Cells preincubated in (10 mu mol l(-1), 32 min) showed essentially homologous desensitisation, and this phenomenon reversed slowly (half-time 6.3+/-0.9 h), After 10 min of recovery from preincubation in adrenaline, isobutylmethylxanthine (IBMX, 5 mmol l(-1)) had no effect upon the desensitisation and the cells showed no loss of sensitivity to ATP and forskolin. After 10 h, however, the persistent desensitisation was partially reversed by IBMX and the cells showed reduced responses to ATP and forskolin, Increased phosphodiesterase activity may thus contribute to the persistent 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 adrenaline but that this second messenger may initiate the series of events leading to the generalised loss of sensitivity seen after 10 h.