Abstract
We characterized inhibition of N-type Ca2+ and M current K+ channels in rat superior cervical ganglion neurons by angiotensin II (angioII) using the patch clamp. Of 120 neurons, 97 showed inhibition of ICa (mean 32%), which was slow in onset and very slow to reverse under whole-cell recording conditions. This inhibition was blocked by the AT1 receptor antagonist losartan, attenuated by inclusion of 2 mM GDP-beta-S in the pipette, mostly pertussis toxin insensitive, half-sensitive to N-ethylmaleimide, and wholly voltage independent. With 20 mM instead of 0.1 mM BAPTA in the pipette, the inhibition was strongly attenuated; however, we detected no angioII-induced [Ca2+]i signal using the fluorescent indicator indo-1. IBa from cell-attached patches was reduced by bath-applied angioII (mean 33%), suggesting use of a diffusible cytoplasmic messenger. M currents were inhibited by angioII in 8 of 11 neurons (mean 50%) cultured overnight. Hence, a second agonist, angioII, may share the slow, second messenger-utilizing, pertussis toxin-insensitive signaling pathway used by muscarinic agonists.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Angiotensin II / pharmacology*
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Angiotensin Receptor Antagonists
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Animals
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Biphenyl Compounds / pharmacology
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Calcium / metabolism*
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Calcium Channels / drug effects
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Calcium Channels / physiology*
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Ethylmaleimide / pharmacology
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Fluorescent Dyes
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GTP-Binding Proteins / metabolism*
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Guanosine Diphosphate / analogs & derivatives
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Guanosine Diphosphate / pharmacology
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Imidazoles / pharmacology
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In Vitro Techniques
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Indoles
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Ion Channels / drug effects
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Ion Channels / physiology*
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Kinetics
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Losartan
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Membrane Potentials / drug effects
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Microscopy, Fluorescence
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Neurons / drug effects
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Neurons / physiology*
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Pertussis Toxin
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Rats
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Rats, Sprague-Dawley
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Second Messenger Systems
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Signal Transduction / drug effects
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Somatostatin / pharmacology
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Superior Cervical Ganglion / physiology*
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Tetrazoles / pharmacology
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Thionucleotides / pharmacology
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Virulence Factors, Bordetella / pharmacology
Substances
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Angiotensin Receptor Antagonists
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Biphenyl Compounds
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Calcium Channels
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Fluorescent Dyes
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Imidazoles
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Indoles
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Ion Channels
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Tetrazoles
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Thionucleotides
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Virulence Factors, Bordetella
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Angiotensin II
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Guanosine Diphosphate
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Somatostatin
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Egtazic Acid
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guanosine 5'-O-(2-thiodiphosphate)
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Pertussis Toxin
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GTP-Binding Proteins
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Losartan
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1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
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indo-1
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Ethylmaleimide
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Calcium