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PMID: 8394568 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Intracellular ATP and GTP are both required to preserve modulation of N-type calcium channel current by norepinephrine.

Pflugers Archiv : European journal of physiology ·Vol. 423 ·No. 5-6 ·1993-06-00 ·Pages 472-9

Elmslie KS, Werz MA, Overholt JL, Jones SW

Abstract

Norepinephrine (NE) inhibits voltage-dependent calcium channels of sympathetic neurons. We investigated the role of intracellular nucleotides in this inhibition for clues to receptor-channel coupling mechanisms. Both ATP and GTP are required to preserve NE responsiveness during whole-cell dialysis. The response to NE was gradually lost in bullfrog sympathetic neurons dialyzed with GTP as the only nucleotide, ATP only, or no nucleotides. Replacing ATP with ATP[gamma-S] resulted in spontaneous modulation of calcium channel current, possibly because of production of GTP[gamma-S]. The nonhydrolyzable ATP analog p[NH]ppA could substitute for ATP to preserve NE responsiveness. The protein phosphatase inhibitors okadaic acid and calyculin-A did not affect NE inhibition of calcium channel current, or recovery from that inhibition. These results suggest protein phosphorylation is not involved in the inhibition of calcium channel current, but binding of ATP to some intracellular site is required for the coupling of adrenergic receptors to calcium channels.

MeSH Terms
Adenosine Triphosphate/analogs & derivatives,pharmacology,physiology Animals Binding Sites/drug effects Calcium Channels/drug effects,metabolism Ethers, Cyclic/pharmacology Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology Guanosine Triphosphate/analogs & derivatives,physiology In Vitro Techniques Kinetics Marine Toxins Neurons/drug effects,metabolism Norepinephrine/pharmacology Okadaic Acid Oxazoles/pharmacology Phosphoprotein Phosphatases/antagonists & inhibitors Rana catesbeiana Sympathetic Nervous System/cytology,metabolism Vasoconstrictor Agents/pharmacology
Chemicals
Calcium Channels Ethers, Cyclic Marine Toxins Oxazoles Vasoconstrictor Agents Okadaic Acid adenosine 5'-O-(3-thiotriphosphate) Guanosine 5'-O-(3-Thiotriphosphate) calyculin A Guanosine Triphosphate Adenosine Triphosphate Phosphoprotein Phosphatases Norepinephrine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Elmslie K S
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106.
Werz M A
Overholt J L
Jones S W
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Article Info
Journal
Pflugers Archiv : European journal of physiology
Abbr.
Pflugers Arch
ISSN
0031-6768
DOI
10.1007/BF00374943
Published
1993-06-00
Pages
472-9
Language
English
Region
Germany
NLM ID
0154720
Subset
IM
Grants
NHLBI NIH HHS · HL 07563 · United States
NINDS NIH HHS · NS 08528 · United States
NINDS NIH HHS · NS 24471 · United States
External Links
PubMed source DOI: 10.1007/BF00374943 View journal details
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