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Cited by 57Receptor Mechanisms and SignalingProtein Kinase Regulation and GTPase SignalingNeuroscience and Neuropharmacology Research

Muscarinic receptor-mediated translocation of calmodulin in SK-N-SH human neuroblastoma cells.

Mangels, L A, Gnegy, M E·1990·Molecular Pharmacology
DOI 10.1016/s0026-895x(25)11051-1
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Abstract

The role of muscarinic receptor-mediated polyphosphoinositide hydrolysis and subsequent calcium signals in altering the subcellular localization of calmodulin (CaM) was examined in SK-N-SH human neuroblastoma cells. Upon incubation of the cells with the full agonist carbachol, a 4.5- to 5-fold increase in CaM in the cytosol was observed, from 126 ng of CaM to 629 ng of CaM. There was an accompanying 68% decrease in membrane-bound CaM. The increase in the cytosol was maximal by 15 min, as was a corresponding decrease in membrane-associated CaM. The redistribution of CaM was maintained for at least 2 hr, before returning toward control levels by 4 hr. The EC50 values for carbachol in eliciting the translocation were 3.7 microM for the increase in cytosol and 1.3 microM for the decrease in membranes. The maximal changes in CaM concentration in both membranes and cytosol occurred with 10 microM carbachol. Incubation of the SK-N-SH cells with the partial muscarinic agonists bethanechol and arecoline resulted in 27 and 26% decreases in membrane-associated CaM, respectively, and 28 and 35% increases in cytosolic CaM, respectively. Thus, the partial agonists were less efficacious than carbachol in eliciting changes in CaM localization. Atropine completely blocked the carbachol-stimulated translocation, whereas the nicotinic agonist 1,1-dimethyl 4-phenylpiperazinium had no effect on the localization of CaM. Activation of receptors coupled to adenylate cyclase did not affect distribution of CaM. CaM content in membranes and cytosol of cells incubated with prostaglandin E1 or the alpha 2-adrenergic agonist UK 14,304 was not different from control values. The ionophore ionomycin (10 microM) and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) (50 nM) were both able to elicit changes in CaM distribution. Ionomycin caused a 64% increase in CaM in the cytosol, with no significant change in membrane CaM. TPA elicited a decrease in membrane-associated CaM, with a corresponding increase in CaM in the cytosol. When TPA and ionomycin were incubated together, the translocation was equal in magnitude to that observed with carbachol alone. The protein kinase C inhibitor H-7 blocked the TPA-stimulated response and partially blocked the carbachol-stimulated response. The CaM-binding protein neuromodulin, which demonstrates a decreased affinity for CaM in the presence of Ca2+ and when phosphorylated by protein kinase C, was present in both membranes and cytosol of SK-N-SH cells.(ABSTRACT TRUNCATED AT 400 WORDS)

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  • In some systems, pathways that stimulate PKC and release bound CaM can potentiate CaMKII.

    “In some systems it has been shown that pathways that stimulate PKC and release bound CaM can potentiate CaMKII (116, 117).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [116]

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Authors
Mangels, L. A., & Gnegy, M. E.
Affiliations
University of Michigan (US)
ORCID
Gnegy, M E
Venue
Molecular Pharmacology
Publisher
Elsevier BV
Published
1990-06
Volume
37
Issue
6
Pages
820-826
ISSN
0026-895X (ISSN-L)
DOI
10.1016/s0026-895x(25)11051-1
OpenAlex
W2297612866
Cited by
57
References
0
Citations by year
2023: 1 · 2017: 1
FWCI
0.84
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Molecular Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed
Funders
  • National Institutes of Health (5r01mh036044-16)
  • National Institute of Mental Health (MH 36044)
  • National Institute of General Medical Sciences (T32GM007767, 2T32 GM07767)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
calmodulin, muscarinic receptors, subcellular translocation, SK-N-SH cells, carbachol, bethanechol, arecoline, atropine, polyphosphoinositide hydrolysis, calcium signaling, ionomycin, phorbol ester, phorbol myristate acetate
MeSH terms
Adenylyl Cyclases, Biological Transport, Calcium, Calmodulin, Carbachol, Humans, Isoquinolines, Kinetics, Neuroblastoma, Piperazines, Receptors, Muscarinic, Tetradecanoylphorbol Acetate, Ionomycin, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

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