Portein kinases in brown adipose tissue of developing rats. State of activation of protein kinase during development and cold exposure and its relationship to adenosine 3':5'-monophosphate, lipolysis, and heat production

Abstract

The addition of norepinephrine to brown fat in vitro produced a dose-dependent increase in the protein kinase activity ratio (the ratio of activity assayed without cAMP to that assayed with cAMP) in extracts subsequently prepared in the presence of 0.5 M NaCl. The ratio was slightly increased by insulin. The effects of norepinephrine were potentiated by theophylline and reduced by propranolol. There was a significant linear regression between protein kinase activity ratio and the rate of glycerol release for ratios between 0.32 and 0.52. Higher activity ratios were associated with a slight but nonsignificant increase in glycerol release. The relationship between the protein kinase activity ratio and the concentration of cAMP in brown fat could be expressed by simple saturation kinetics. There was a significant linear regression between the reciprocal of the concentration of cAMP in the tissue and the reciprocal of the activity ratio over the whole range of observed values. Exposure of 1-month-old rats to cold increased the protein kinase activity ratio in their brown fat. This confirms that activation of protein kinase is involved in the physiological response of a tissue to a specific environmental stimulus. As the rat became fully adapted to the cold, the activity ratio declined. The protein kinase activity ratio in brown fat was low in late fetuses but greatly increased immediately after birth and remained high for the next 2 weeks. During this period the ratio was not further increased by the injection of norepinephrine but was reduced after chemical sympathectomy. The activity ratio in brown fat fell during the 3rd and 4th weeks after birth. At this time injection of norepinephrine increased the ratio whereas chemical sympathectomy had little effect. These observations confirm that the stimulation of the tissue by the sympathetic nerves results in an activation of protein kinase and reflect the reduced requirement for heat production in brown fat as the animals grow.