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PMID: 1718001 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Inhibition of cAMP accumulation by intracellular calcium mobilization in C6-2B cells stably transfected with substance K receptor cDNA.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 88 ·No. 20 ·1991-10-15 ·Pages 9257-61

DeBernardi MA, Seki T, Brooker G

Abstract

C6-2B rat glioma cells were stably transfected with substance K receptor cDNA and used to study interactions between cAMP and Ca2+ signaling pathways. Activation of the newly expressed receptors by substance K increased the intracellular free Ca2+ concentration, as monitored by single-cell fura-2 imaging, and markedly inhibited agonist-stimulated cAMP accumulation. Blockade of intracellular Ca2+ mobilization abolished the substance K receptor-mediated inhibition of isoproterenol-induced cAMP production. Phosphodiesterase inhibitors, down-regulation or inhibition of protein kinase C, and pertussis toxin failed to prevent substance K-induced inhibition of agonist-stimulated cAMP accumulation. An increased intracellular Ca2+ concentration caused by either calcium ionophores or activation of endogenous bradykinin receptors was found to markedly reduce cAMP production in wild-type cells. These results demonstrate that elevated intracellular Ca2+ concentration can negatively modulate agonist-stimulated adenylate cyclase activity in C6-2B glioma cells.

MeSH Terms
1-Methyl-3-isobutylxanthine/pharmacology 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone/pharmacology Adenylyl Cyclases/metabolism Animals Bradykinin/pharmacology Calcimycin/pharmacology Calcium/physiology Cattle Cell Line Cholera Toxin/pharmacology Cyclic AMP/metabolism DNA/genetics Glioma Isoproterenol/pharmacology Kinetics Neurokinin A/metabolism,pharmacology RNA, Messenger/genetics Rats Receptors, Neurokinin-2 Receptors, Neurotransmitter/drug effects,genetics,physiology Signal Transduction/drug effects Transfection
Chemicals
RNA, Messenger Receptors, Neurokinin-2 Receptors, Neurotransmitter 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone Calcimycin Neurokinin A DNA Cholera Toxin Cyclic AMP Adenylyl Cyclases Isoproterenol Bradykinin Calcium 1-Methyl-3-isobutylxanthine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
DeBernardi M A
Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, Washington, DC 20007.
Seki T
Brooker G
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.88.20.9257
Published
1991-10-15
Pages
9257-61
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC52693
Subset
IM
Grants
NHLBI NIH HHS · HL 28940 · United States
External Links
PubMed source DOI: 10.1073/pnas.88.20.9257 PMC Full Text View journal details
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