Hormonal regulation of chick kidney inhibitor of adenosine 3',5'-monophosphate-dependent protein kinase

The endogenous inhibitor of cAMP-dependent protein kinase (PKI) in chick kidney is regulated by the vitamin D status of the animal. To determine the specific factors that are involved in the regulation of chick kidney PKI, chicks were raised on a low (0.05%), normal (1%), or high (3%) calcium diet and given vitamin D3 or vehicle three times a week orally. The results from this experimental protocol show that vitamin D3 or one or more of its metabolites and serum calcium levels are both involved in the regulation of chick kidney PKI in vivo. Measurement of PKI activity in primary cultures of chick kidney cells revealed treatment with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3) led to a 90-95% decrease in PKI activity. This effect of 1,25-(OH)2D3 was dose dependent, and neither PTH nor insulin was able to reverse it completely. Treatment with PTH caused 30-60% increase in PKI activity, and cell cultures that were grown in medium containing either 0.5 or 2 mM calcium chloride had similar PKI activities. Taken together, these results indicate that 1,25-(OH)2D3, the most physiologically active form of vitamin D3, is the predominant regulator of PKI, but serum calcium, indirectly through the regulation of PTH secretion, is also involved.