Document Detail

Functional studies with substance P analogues: effects of N-terminal, C-terminal, and C-terminus-extended analogues of substance P on nicotine-induced secretion and desensitization in cultured bovine adrenal chromaffin cells.
MedLine Citation:
PMID:  7514649     Owner:  NLM     Status:  MEDLINE    
Substance P (SP) and SP analogues, including C-terminal, N-terminal, and C-terminus-extended analogues, have been investigated for their ability to modulate nicotine-induced secretion from bovine adrenal chromaffin cells in culture. Secretion was monitored by measuring the release of endogenous catecholamines by electrochemical detection following separation on HPLC and the release of endogenous ATP with an on-line luciferin-luciferase bioluminescence technique. SP is known to have the following two effects on nicotine-induced secretion of catecholamines (see Livett and Zhou, 1991): inhibition of the nicotinic response and protection against nicotinic desensitization. Secretion induced by 10(-5) M nicotine was inhibited 70-80% by SP, SP-methyl ester, and the C-terminus-extended analogue SP-Tyr12-NH2, 65% by (Ala3)SP-NH2, 45% by the C-terminal analogue SP(4-11), and 20 and 5% by the N-terminal analogues SP(1-7) and SP(1-5), respectively, when these peptides were present at 3 x 10(-5) M concentrations. The order of potency was SP = SP-methyl ester = SP-Tyr12-NH2 > (Ala3)SP-NH2 > SP(4-11) > SP(1-7) > SP(1-5). SP, SP-methyl ester, and (Ala3)SP-NH2 protected against nicotinic desensitization by 40-55%, and SP(4-11) protected by 20% (all at 3 x 10(-5) M). In contrast, the N-terminal analogues SP(1-7) and SP(1-5) and the C-terminus-extended analogue SP-Tyr12-NH2 at 3 x 10(-5) M did not protect against nicotinic desensitization. Cyclo-SP(3-9), Ac-SP(3-9)-NH2, SP(3-9), and SP(3-6) had neither inhibitory nor facilitatory effects on secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
N S Cheung; P Karlsson; J X Wang; M Bienert; P Oehme; B G Livett
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  62     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  1994 Jun 
Date Detail:
Created Date:  1994-06-21     Completed Date:  1994-06-21     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2246-53     Citation Subset:  IM    
Department of Biochemistry, University of Melbourne, Parkville, Victoria, Australia.
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MeSH Terms
Adenosine Triphosphate / metabolism
Adrenal Glands / cytology,  drug effects,  secretion*
Amino Acid Sequence
Cells, Cultured
Chemical Phenomena
Chromaffin System / cytology,  drug effects,  secretion*
Molecular Sequence Data
Nicotine / pharmacology*
Substance P / analogs & derivatives*,  pharmacology
Reg. No./Substance:
33507-63-0/Substance P; 54-11-5/Nicotine; 56-65-5/Adenosine Triphosphate

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