Document Detail

Actions of somatostatins on gastric smooth muscle cells.
MedLine Citation:
PMID:  1347975     Owner:  NLM     Status:  MEDLINE    
The effects of somatostatin-28, somatostatin-14, and a synthetic somatostatin octapeptide analogue, D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Cys-Nal-NH2 (cyclo SS-8) were examined on contraction of dispersed gastric smooth muscle cells from guinea pigs. The somatostatins did not cause contraction of gastric smooth muscle cells, nor did they inhibit carbachol-stimulated contraction. However, they reversed vasoactive intestinal peptide (VIP)-induced inhibition (relaxation) of carbachol-stimulated contraction. Somatostatin-28 had a half-maximal effect (EC50) at 1.6 +/- 0.8 nM, cyclo SS-8 at 0.6 +/- 0.3 nM, but somatostatin-14 had no effect even when used in concentrations as high as 1 microM. Incubation of muscle cells with peptidase inhibitors phosphoramidon (1 microM) plus amastatin (10 microM) had no effect on the EC50 of somatostatin-28 or cyclo SS-8 but increased the potency of somatostatin-14 greater than 1,000-fold. When peptides were incubated with muscle cells and the products applied to high-performance liquid chromatography, cyclo SS-8 was not degraded, but somatostatin-14 was rapidly degraded when present alone, and the addition of peptidase inhibitors partially inhibited the degradation. Cyclo SS-8 had its maximal effect at 0.5-1 min and inhibited relaxation induced by VIP, isoproterenol, glucagon, or dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP). Cyclo SS-8 partially inhibited the increase in VIP-stimulated cAMP. Preincubation with pertussis toxin blocked the inhibitory action of cyclo SS-8 on VIP or DBcAMP-induced relaxation. These results indicate that gastric smooth muscle cells rapidly degrade somatostatin-14 and suggest that muscle cell peptidases could have a major effect on the actions of somatostatin-14.(ABSTRACT TRUNCATED AT 250 WORDS)
Z F Gu; T Pradhan; D H Coy; S Mantey; N W Bunnett; R T Jensen; P N Maton
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  262     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1992 Mar 
Date Detail:
Created Date:  1992-04-23     Completed Date:  1992-04-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  G432-8     Citation Subset:  IM    
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
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MeSH Terms
Amino Acid Sequence
Bucladesine / pharmacology
Carbachol / pharmacology
Cyclic AMP / metabolism
Dose-Response Relationship, Drug
Glucagon / pharmacology
Guinea Pigs
Isoproterenol / pharmacology
Molecular Sequence Data
Muscle Contraction / physiology
Muscle, Smooth / physiology*
Octreotide / analogs & derivatives*,  pharmacology
Protein Precursors / physiology
Somatostatin / analogs & derivatives,  physiology*
Stomach / drug effects,  physiology*
Vasoactive Intestinal Peptide / pharmacology
Grant Support
Reg. No./Substance:
0/Protein Precursors; 138248-87-0/phenylalanyl-cysteinyl-tyrosyl-tryptophyl-lysyl-threonyl-cysteinyl-N-naphthylalanine amide; 362-74-3/Bucladesine; 37221-79-7/Vasoactive Intestinal Peptide; 51-83-2/Carbachol; 51110-01-1/Somatostatin; 60-92-4/Cyclic AMP; 75037-27-3/Somatostatin-28; 7683-59-2/Isoproterenol; 83150-76-9/Octreotide; 9007-92-5/Glucagon

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