Somatostatin: selective inhibition of cyclic AMP stimulated protein kinase.
Utilizing histones as a substrate and measuring the production of labelled phosphoserine from [gamma 32P-ATP], cAMP stimulated protein kinase activity was found in islet and anterior pituitary secretory vesicles. Cyclic AMP (5 X 10(-7)m)stimulated islet secretory vesicle protein kinase activity as evidenced by a net  increase of 32P incorporation into phosphoserine 7.35 +/- 1.68 pmoles/micrograms, (P LESS THAN 9001). Somatostatin (0.1 ng/microgram) decreased 32P phosphoserine production from 10.64 +/- 1.72 to 5.61 +/- 1.26 pmoles/microgram (Pless than .01) by suppressing cAMP stimulated protein kinase activity. In pituitary secretory vesicles, cAMP (5 X 10(-6M) increased 32P incorporation into TCA precipitable protein from 127.3 +/- 8.6 to 202.6 +/- 12.5 pmoles/microgram, P less than .001. With somatostatin (0.2 ng/microgram) there was 55.25+/- 1.95% inhibition of cAMP stimulated protein kinase activity, (P LESS THAN .001). Somatostatin did not inhibit cAMP stimulated protein kinase activity in erythrocyte membrane ghosts nor did somatostatin inhibit the partially purified cAMP dependent protein kinase from cardiac muscle. These data suggest that either (1) a specific somatostatin sensitive dependent protein kinase is present in islet and anterior pituitary secretory vesicles or (2) that a somatostatin receptor is present in these tissues which allows somatostatin to act selectively at these sites. Somatostatin may act by inhibiting the cAMP dependent protein kinase enzme in certain key tissues or subcellular organelles.
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D007515:Islets of Langerhans / Q000201:enzymology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010902:Pituitary Gland / Q000201:enzymology; D047428:Protein Kinase Inhibitors; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology*
D006657:Histones; D008565:Membrane Proteins; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D013004:Somatostatin; D000242:Cyclic AMP