ADRENALINE-INDUCED DESENSITIZATION OF LIVER ADENYLATE-CYCLASE

The densitization of rat liver adenylate cyclase by adrenaline treatment of liver slices was demonstrated. Partial desensitization of adenylate cyclase to adrenaline could be achieved by preincubation of liver slices with 10-5 M adrenaline provided albumin was included in the buffer. No effect was seen in the absence of albumin, and glucagon sensitivity of the enzymes remained unaffected. When desensitized slices, treated for 60 min with 10-5 M adrenaline, were washed several times to remove the hormone and reincubated for periods up to 90 min, no significant recovery of the adrenaline sensitivity of adenylate cyclase was observed. At 10-6 M adrenaline desensitization was notable, and at 105-104 M it became maximal, representing a 50-75% loss of hormone sensitivity compared to controls. Within 30 min an almost maximal effect was obtained. Incubations of more than 90 min led to notable physical deterioration of the slices. In some experiments there was a drop in basal activity or yield and of hormone sensitivity of the enzyme after 60-90 min of incubating slices in the absence of adrenaline; however, these changes were below 10% of the control values at zero time, and the effect of adrenaline treatment on the hormone sensitivity of the enzyme was always significant compared to control slice incubations of the same duration. The sensitivity of the adenylate cyclase to glucagon was not changed in any of these experiments. The mechanism underlying hormone-induced desensitization of adenylate cyclase is not known.