Korean J Physiol Pharmacol.  1997 Oct;1(5):485-493.

alpha-Adrenergic and cholinergic receptor agonists modulate voltage-gated Ca2+ channels

Affiliations
  • 1Department of Physiology, College of Veterinary Medicine.
  • 2Department of Pharmacology, College of Medicine, Chonnam National University, Kwangju 500-757, South Korea.
  • 3Department of Veterinary Medicine, Kangwon National University, Chuncheon, South Korea.

Abstract

We investigated the effect of alpha-adrenergic and cholinergic receptor agonists on Ca2+ current in adult rat trigeminal ganglion neurons using whole-cell patch clamp methods. The application of acetylcholine, carbachol, and oxotremorine (50 muM each) produced a rapid and reversible reduction of the Ca2+ current by 17+/-6%, 19+/-3% and 18+/-4%, respectively. Atropine, a muscarinic antagonist, blocked carbachol-induced Ca2+ current inhibition to 3 +/- 1%. Norepinephrine (50 muM) reduced Ca2+ current by 18 +/- 2%, while clonidine (50 muM), an alpha2-adrenergic receptor agonist, inhibited Ca2+ current by only 4 +/- 1%. Yohimbine, an alpha2-adrenergic receptor antagonist, did not block the inhibitory effect of norepinephrine on Ca2+ current, whereas prazosin, an alpha1-adrenergic receptor antagonist, attenuated the inhibitory effect of norepinephrine on Ca2+ current to 6 +/- 1%. This pharmacology contrasts with alpha2-adrenergic receptor modulation of Ca2+ channels in rat sympathetic neurons, which is sensitive to clonidine and blocked by yohimbine. Our data suggest that the modulation of voltage dependent Ca2+ channel by norepinephrine is mediated via an alpha1-adrenergic receptor. Pretreatment with pertussis toxin (250 ng/ml) for 16 h greatly reduced norepinephrine- and carbachol-induced Ca2+ current inhibition from 17 +/- 3% and 18 +/- 3% to 2 +/- 1% and 2 +/- 1%, respectively. These results demonstrate that norepinephrine, through an alpha1-adrenergic receptor, and carbachol, through a muscarinic receptor, inhibit Ca2+ currents in adult rat trigeminal ganglion neurons via pertussis toxin sensitive GTP-binding proteins.

Keyword

alpha-adrenergic receptor and muscarinic receptor; Ca2+ currents; Pertussis toxin-sensitive GTP binding proteins; Rat trigeminal ganglion neurons

MeSH Terms

Acetylcholine
Adult
Animals
Atropine
Carbachol
Clonidine
GTP-Binding Proteins
Humans
Neurons
Norepinephrine
Oxotremorine
Pertussis Toxin
Pharmacology
Prazosin
Rats
Receptors, Muscarinic
Trigeminal Ganglion
Yohimbine
Acetylcholine
Atropine
Carbachol
Clonidine
GTP-Binding Proteins
Norepinephrine
Oxotremorine
Pertussis Toxin
Prazosin
Receptors, Muscarinic
Yohimbine
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