Studies on the intracellular mechanism of action of alpha-melanocyte-stimulating hormone on rat adrenal zona glomerulosa.
The intracellular mechanisms of action of alpha-MSH in rat adrenocortical cells were examined. When rat adrenal capsule (largely glomerulosa) cells were stimulated with a range of concentrations of alpha-MSH there was significant stimulation of aldosterone secretion at 10(-10) mol/l, although cyclic AMP was not increased until high concentrations of alpha-MSH were used (10(-6) mol/l and above). However, cells incubated with ACTH showed an increase in aldosterone secretion at 10(-11) mol/l and levels of cyclic AMP were elevated at 10(-9) mol ACTH/l. When rat adrenal whole capsules were incubated with alpha-MSH, membrane-bound protein kinase C (PKC) activity was increased and cytosolic enzyme activity decreased, showing PKC activation. Stimulation with angiotensin II also induced translocation of PKC activity, but ACTH did not. When [3H]inositol-loaded glomerulosa cells were stimulated with alpha-MSH there was significant generation of [3H]inositol trisphosphate (IP3) at concentrations of alpha-MSH which stimulated secretion of aldosterone. Significantly increased levels of [3H]IP3 were also measured when loaded cells were exposed to angiotensin II. ACTH did not cause any significant stimulation of [3H]IP3 production at any concentration used. These results indicate that activation of PKC and phospholipase C is important in modulating the steroidogenic effect of alpha-MSH.
Kapas
S
S
Department of Biochemistry, Faculty of Basic Medical Sciences, Queen Mary and Westfield College, London, U.K.
Orford
C D
CD
Barker
S
S
Vinson
G P
GP
Hinson
J P
JP
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D000242:Cyclic AMP / Q000502:physiology; D004789:Enzyme Activation; D005260:Female; D007295:Inositol Phosphates / Q000096:biosynthesis; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000521:alpha-MSH / Q000502:physiology*
D007295:Inositol Phosphates; D000804:Angiotensin II; D000450:Aldosterone; D000521:alpha-MSH; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D011493:Protein Kinase C