Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined the ability of protein kinase C (PKC) to induce heterologous desensitization by targeting specific G proteins and limiting their ability to transduce signals in smooth muscle. Activation of PKC by pretreatment of intestinal smooth muscle cells with phorbol 12-myristate 13-acetate, cholecystokinin octapeptide, or the phosphatase 1 and phosphatase 2A inhibitor, calyculin A, selectively phosphorylated Galpha(i-1) and Galpha(i-2), but not Galpha(i-3) or Galpha(o), and blocked inhibition of adenylyl cyclase mediated by somatostatin receptors coupled to G(i-1) and opioid receptors coupled to G(i-2), but not by muscarinic M(2) and adenosine A(1) receptors coupled to G(i-3). Phosphorylation of Galpha(i-1) and Galpha(i-2) and blockade of cyclase inhibition were reversed by calphostin C and bisindolylmaleimide, and additively by selective inhibitors of PKCalpha and PKCepsilon. Blockade of inhibition was prevented by downregulation of PKC. Phosphorylation of Galpha-subunits by PKC also affected responses mediated by betagamma-subunits. Pretreatment of muscle cells with cANP-(4-23), a selective agonist of the natriuretic peptide clearance receptor, NPR-C, which activates phospholipase C (PLC)-beta3 via the betagamma-subunits of G(i-1) and G(i-2), inhibited the PLC-beta response to somatostatin and [D-Pen(2,5)]enkephalin. The inhibition was partly reversed by calphostin C. Short-term activation of PKC had no effect on receptor binding or effector enzyme (adenylyl cyclase or PLC-beta) activity. We conclude that selective phosphorylation of Galpha(i-1) and Galpha(i-2) by PKC partly accounts for heterologous desensitization of responses mediated by the alpha- and betagamma-subunits of both G proteins. The desensitization reflects a decrease in reassociation and thus availability of heterotrimeric G proteins.
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PMID:Heterologous desensitization of response mediated by selective PKC-dependent phosphorylation of G(i-1) and G(i-2). 1100 72

Atrial natriuretic peptide (ANP) is present in gastric mucosa and preferentially binds to two subtypes of natriuretic peptide receptors (NPR), NPR-A and NPR-C. The present study examines the role of endogenous ANP in regulating endocrine secretion in rat and human stomachs. NPR-A protein expression and transcripts were identified in rat antral and fundic mucosa by Western blot and RT-PCR. In superfused rat and human antral and fundic segments, ANP (0.1 pM to 0.1 microM) caused a concentration-dependent increase in somatostatin secretion. In antrum, this was accompanied by a decrease in gastrin, and in fundus, this was accompanied by a decrease in histamine secretion. Changes in gastrin and histamine secretion reflected changes in somatostatin secretion and were abolished by somatostatin antibody. The NPR-A receptor antagonist anantin 1) inhibited basal somatostatin secretion and 2) abolished the somatostatin, gastrin, and histamine responses to ANP. We conclude that endogenous ANP, acting via the NPR-A receptor, stimulates somatostatin secretion from both antrum and fundus of rat and human stomach. Stimulation of somatostatin secretion is coupled to inhibition of gastrin secretion in the antrum and inhibition of histamine secretion in the fundus.
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PMID:Gastric atrial natriuretic peptide regulates endocrine secretion in antrum and fundus of human and rat stomach. 1263 61