[Leu]enkephalin stimulates carbohydrate metabolism in isolated hepatocytes and kidney tubule fragments by interaction with angiotensin II receptors.
The possibility that the effects of [Leu]enkephalin in vitro on hepatic carbohydrate metabolism are mediated by interaction with angiotensin II receptors has been examined. Preincubation of hepatocytes with either the angiotensin II receptor antagonist [Sar1,Ile8]angiotensin II or 10 mM-dithiothreitol abolished the ability of both angiotensin II and [Leu]enkephalin to increase phosphorylase a in hepatocytes prepared from fed rats. Dithiothreitol had no effect on the stimulation of phosphorylase in the presence of glucagon or phenylephrine, although it also inhibited the response to vasopressin. [Leu]enkephalin displaced specifically bound 125I-labelled angiotensin II from hepatic plasma membranes over a concentration range of 10(-7)-10(-5) M. This correlated with the dose-response required to stimulate phosphorylase activity in intact hepatocytes and suggests that the effects of the opioid peptides on carbohydrate metabolism in liver are the result of cross-reactivity of the peptides with angiotensin II receptors. Addition of 10(-5) M-[Leu]enkephalin to isolated kidney tubule fragments stimulated gluconeogenesis from 5 mM-pyruvate, the magnitude of stimulation being comparable to that by either angiotensin II or adrenaline. This effect of the opioid peptide was also abolished by pretreatment of the tubules with [Sar1,Ile8]angiotensin II, suggesting that the ability of [Leu]enkephalin to interact with angiotensin II receptors is not restricted to the liver, but may occur in other tissues where both receptors occur together.
Hothi
S K
SK
School of Biological Sciences, University of Sussex, Brighton, U.K.
Randall
D P
DP
Titheradge
M A
MA
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D050260:Carbohydrate Metabolism; D002462:Cell Membrane / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000494:pharmacology*; D005943:Gluconeogenesis; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010762:Phosphorylase a / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism*
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D004743:Enkephalin, Leucine; D010762:Phosphorylase a; D004229:Dithiothreitol