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Calcium channels at the adrenergic neuroeffector junction in the rabbit ear artery

Zygmunt, P M LU and Högestätt, E D LU (1993) In Naunyn-Schmiedeberg's Archives of Pharmacology 347(6). p.23-617
Abstract

Neurotransmitter release is dependent on influx of Ca2+ through voltage-operated calcium channels (VOCCs). These channels may be divided into L, N, T and P subtypes. To investigate the subtypes of VOCC involved in transmitter release from adrenergic nerves in the isolated rabbit ear artery, the effects of some subtype selective VOCC antagonists were examined on contractile responses induced by electrical field stimulation (EFS), and exposure to an isosmolar (low Na+, normal Cl- content) or a hyperosmolar (normal Na+, high Cl- content) 60 mM K+ solution. Tetrodotoxin (TTX) and the L channel blocker nimodipine were present in the latter experiments to inhibit sodium-dependent action potential discharge and the direct contractile effect of... (More)

Neurotransmitter release is dependent on influx of Ca2+ through voltage-operated calcium channels (VOCCs). These channels may be divided into L, N, T and P subtypes. To investigate the subtypes of VOCC involved in transmitter release from adrenergic nerves in the isolated rabbit ear artery, the effects of some subtype selective VOCC antagonists were examined on contractile responses induced by electrical field stimulation (EFS), and exposure to an isosmolar (low Na+, normal Cl- content) or a hyperosmolar (normal Na+, high Cl- content) 60 mM K+ solution. Tetrodotoxin (TTX) and the L channel blocker nimodipine were present in the latter experiments to inhibit sodium-dependent action potential discharge and the direct contractile effect of K+ depolarization on the smooth muscle cells. Prazosin abolished the contractile effect of EFS, indicating that the response was elicited by activation of adrenergic nerves. The EFS-induced contractions were concentration-dependently inhibited by the N channel blocker omega-conotoxin (pIC50 = 9.0) and the proposed L channel blocker T-cadinol (pIC50 = 4.5), while nimodipine and the T channel blocker tetramethrin had no effect. The isosmolar and hyperosmolar K+ solutions induced a prazosin-sensitive contraction, amounting to 46% and 10% of the response to 10(-5) M noradrenaline (NA), respectively. omega-Conotoxin inhibited the contractile response to the hyperosmolar K+ solution, but not that to the isosmolar K+ solution. T-cadinol preferentially inhibited the response to the hyperosmolar K+ solution. Tetramethrin had no effect on contractions induced by either type of K+ solution.(ABSTRACT TRUNCATED AT 250 WORDS)

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keywords
Animals, Arteries/metabolism, Calcium Channel Blockers/pharmacology, Calcium Channels/drug effects, Ear/blood supply, Electric Stimulation, Female, In Vitro Techniques, Male, Muscle Contraction/drug effects, Muscle, Smooth, Vascular/drug effects, Neuroeffector Junction/drug effects, Nimodipine/pharmacology, Norepinephrine/pharmacology, Peptides/pharmacology, Potassium Chloride/pharmacology, Prazosin/pharmacology, Pyrethrins/pharmacology, Rabbits, Regional Blood Flow/physiology, Sesquiterpenes/pharmacology, Sympathetic Nervous System/drug effects, Tetrodotoxin/pharmacology, omega-Conotoxins
in
Naunyn-Schmiedeberg's Archives of Pharmacology
volume
347
issue
6
pages
7 pages
publisher
Springer
external identifiers
  • scopus:0027253952
ISSN
0028-1298
DOI
10.1007/BF00166944
language
English
LU publication?
yes
id
7b10d68e-9e36-410a-a97e-9a0d0403f7dc
date added to LUP
2019-02-20 10:03:20
date last changed
2019-02-24 04:57:32
@article{7b10d68e-9e36-410a-a97e-9a0d0403f7dc,
  abstract     = {<p>Neurotransmitter release is dependent on influx of Ca2+ through voltage-operated calcium channels (VOCCs). These channels may be divided into L, N, T and P subtypes. To investigate the subtypes of VOCC involved in transmitter release from adrenergic nerves in the isolated rabbit ear artery, the effects of some subtype selective VOCC antagonists were examined on contractile responses induced by electrical field stimulation (EFS), and exposure to an isosmolar (low Na+, normal Cl- content) or a hyperosmolar (normal Na+, high Cl- content) 60 mM K+ solution. Tetrodotoxin (TTX) and the L channel blocker nimodipine were present in the latter experiments to inhibit sodium-dependent action potential discharge and the direct contractile effect of K+ depolarization on the smooth muscle cells. Prazosin abolished the contractile effect of EFS, indicating that the response was elicited by activation of adrenergic nerves. The EFS-induced contractions were concentration-dependently inhibited by the N channel blocker omega-conotoxin (pIC50 = 9.0) and the proposed L channel blocker T-cadinol (pIC50 = 4.5), while nimodipine and the T channel blocker tetramethrin had no effect. The isosmolar and hyperosmolar K+ solutions induced a prazosin-sensitive contraction, amounting to 46% and 10% of the response to 10(-5) M noradrenaline (NA), respectively. omega-Conotoxin inhibited the contractile response to the hyperosmolar K+ solution, but not that to the isosmolar K+ solution. T-cadinol preferentially inhibited the response to the hyperosmolar K+ solution. Tetramethrin had no effect on contractions induced by either type of K+ solution.(ABSTRACT TRUNCATED AT 250 WORDS)</p>},
  author       = {Zygmunt, P M and Högestätt, E D},
  issn         = {0028-1298},
  keyword      = {Animals,Arteries/metabolism,Calcium Channel Blockers/pharmacology,Calcium Channels/drug effects,Ear/blood supply,Electric Stimulation,Female,In Vitro Techniques,Male,Muscle Contraction/drug effects,Muscle, Smooth, Vascular/drug effects,Neuroeffector Junction/drug effects,Nimodipine/pharmacology,Norepinephrine/pharmacology,Peptides/pharmacology,Potassium Chloride/pharmacology,Prazosin/pharmacology,Pyrethrins/pharmacology,Rabbits,Regional Blood Flow/physiology,Sesquiterpenes/pharmacology,Sympathetic Nervous System/drug effects,Tetrodotoxin/pharmacology,omega-Conotoxins},
  language     = {eng},
  number       = {6},
  pages        = {23--617},
  publisher    = {Springer},
  series       = {Naunyn-Schmiedeberg's Archives of Pharmacology},
  title        = {Calcium channels at the adrenergic neuroeffector junction in the rabbit ear artery},
  url          = {http://dx.doi.org/10.1007/BF00166944},
  volume       = {347},
  year         = {1993},
}