Adenosine 5?-Monophosphate Is a Selective Inhibitor of the Brown Adipocyte Nonselective Cation Channel

Adenosine 5?-Monophosphate Is a Selective Inhibitor of the Brown Adipocyte Nonselective Cation... Calcium-activated nonselective cation channels (NSCCa) in brown adipocytes are inhibited by several nucleotides acting on the cytosolic side of the membrane. We used excised inside-out patches from rat brown adipocytes to identify important nucleotide structures for NSC-channel inhibition. We found that 100 mM 5?-AMP inhibited NSC-channel activity more than did ATP or ADP. Adenosine was a weak inhibitor, whereas adenine and ribose-5-phosphate had no effect. The channel activity was effectively blocked by 10 mM AMP, but it was unaffected by 10 mM cAMP, CMP, GMP, IMP, TMP or UMP. Dose-response studies yielded IC50-values of 4 mM for AMP and 32 mM for cAMP. dAMP was as effective as AMP, but all 5?-phosphate group modifications on AMP dramatically lowered the inhibitory effect. 10 mM of the AMP precursor adenylosuccinate weakly inhibited the channel activity. An increase in AMP concentration from 1 to 10 mM shifted the EC50 for Ca2+ activation almost 1 order of magnitude; a Schild plot analysis yielded a KB value of 0.3 mM for AMP. We conclude that AMP is the most efficacious endogenous nucleotide inhibitor of the brown adipocyte nonselective cation channel (NSCCa/AMP) yet identified and that there is functional competition between Ca2+ and AMP. The brown adipocyte NSCCa/AMP thus appears to be functionally different from the NSCCa,PKA in the exocrine pancreas and the NSCCa,cAMP in the endocrine pancreas, but similar to the NSCCa/AMP in the endocrine pancreas. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Adenosine 5?-Monophosphate Is a Selective Inhibitor of the Brown Adipocyte Nonselective Cation Channel

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Publisher
Springer-Verlag
Copyright
Copyright © 2002 by Springer-Verlag New York Inc.
Subject
Life Sciences; Biochemistry, general; Human Physiology
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-001-0184-0
Publisher site
See Article on Publisher Site

Abstract

Calcium-activated nonselective cation channels (NSCCa) in brown adipocytes are inhibited by several nucleotides acting on the cytosolic side of the membrane. We used excised inside-out patches from rat brown adipocytes to identify important nucleotide structures for NSC-channel inhibition. We found that 100 mM 5?-AMP inhibited NSC-channel activity more than did ATP or ADP. Adenosine was a weak inhibitor, whereas adenine and ribose-5-phosphate had no effect. The channel activity was effectively blocked by 10 mM AMP, but it was unaffected by 10 mM cAMP, CMP, GMP, IMP, TMP or UMP. Dose-response studies yielded IC50-values of 4 mM for AMP and 32 mM for cAMP. dAMP was as effective as AMP, but all 5?-phosphate group modifications on AMP dramatically lowered the inhibitory effect. 10 mM of the AMP precursor adenylosuccinate weakly inhibited the channel activity. An increase in AMP concentration from 1 to 10 mM shifted the EC50 for Ca2+ activation almost 1 order of magnitude; a Schild plot analysis yielded a KB value of 0.3 mM for AMP. We conclude that AMP is the most efficacious endogenous nucleotide inhibitor of the brown adipocyte nonselective cation channel (NSCCa/AMP) yet identified and that there is functional competition between Ca2+ and AMP. The brown adipocyte NSCCa/AMP thus appears to be functionally different from the NSCCa,PKA in the exocrine pancreas and the NSCCa,cAMP in the endocrine pancreas, but similar to the NSCCa/AMP in the endocrine pancreas.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Mar 18, 2014

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