Glyceryl nonivamide

A capsaicin derivative with cardiac calcitonin gene-related peptide releasing, K+ channel opening and vasorelaxant properties

Yi Ching Lo, Jiunn Ren Wu, Sheng-Nan Wu, Ing Jun Chen

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

In this study, the aorta vasorelaxant, coronary calcitonin gene-related peptide (CGRP) releasing, and atrial contractility effects of glyceryl nonivamide (GLNVA) were investigated in guinea pigs. In the isolated thoracic aorta, although GLNVA (0.01-50 μM) concentration dependently induced endothelium-independent relaxations and relaxed phenylephrine-(1.0 μM) induced contractions, it failed to relax 80 mM KCl-induced contractions. The GLNVA (1.0 μM) relaxation response in the aorta was significantly inhibited by tetraethylammonium (2.5-10 mM) or ouabain (5.0 μM) and was attenuated by increased extracellular potassium gradient (10-30 mM). Glibenclamide (0.01- 10 μM) dose dependently antagonized the GLNVA relaxant effect. In the isolated perfused guinea pig heart, GLNVA (0.1-10 μM) increased CGRP-like immunoreactivity outflow from coronary circulation in a concentration- dependent manner. In the isolated right and left guinea pig atria, GLNVA (0.01-10 μM) produced concentration-dependent positive inotropic and chronotropic effects, but these effects were inhibited by pretreatments with ruthenium red (1.0 μM), capsazepine (10 μM), human calcitonin-gene-related peptide (CGRP8-37) (1.0 μM) and sensory neuron denervation, respectively. Based on these findings, we suggest that CGRP may be released by GLNVA from cardiovascular sensory neuron, and it then activates CGRP receptors on the coronary artery and atrium. The GLNVA-induced vasorelaxant effect in the vascular smooth muscle of the aorta is due to CGRP release associated K+ channel opening, and this effect eliminates capsaicin-derived excitability-associated K+ channel blocking activities.

Original languageEnglish
Pages (from-to)253-260
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume281
Issue number1
Publication statusPublished - 1997 May 24

Fingerprint

Calcitonin Gene-Related Peptide
Capsaicin
Vasodilator Agents
Aorta
Guinea Pigs
Sensory Receptor Cells
Calcitonin Gene-Related Peptide Receptors
Ruthenium Red
Coronary Circulation
Tetraethylammonium
N-(4-O-glycerol-3-methoxybenzyl)nonivamide
Glyburide
Phenylephrine
Denervation
Ouabain
Thoracic Aorta
Vascular Smooth Muscle
Endothelium
Coronary Vessels
Potassium

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

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title = "Glyceryl nonivamide: A capsaicin derivative with cardiac calcitonin gene-related peptide releasing, K+ channel opening and vasorelaxant properties",
abstract = "In this study, the aorta vasorelaxant, coronary calcitonin gene-related peptide (CGRP) releasing, and atrial contractility effects of glyceryl nonivamide (GLNVA) were investigated in guinea pigs. In the isolated thoracic aorta, although GLNVA (0.01-50 μM) concentration dependently induced endothelium-independent relaxations and relaxed phenylephrine-(1.0 μM) induced contractions, it failed to relax 80 mM KCl-induced contractions. The GLNVA (1.0 μM) relaxation response in the aorta was significantly inhibited by tetraethylammonium (2.5-10 mM) or ouabain (5.0 μM) and was attenuated by increased extracellular potassium gradient (10-30 mM). Glibenclamide (0.01- 10 μM) dose dependently antagonized the GLNVA relaxant effect. In the isolated perfused guinea pig heart, GLNVA (0.1-10 μM) increased CGRP-like immunoreactivity outflow from coronary circulation in a concentration- dependent manner. In the isolated right and left guinea pig atria, GLNVA (0.01-10 μM) produced concentration-dependent positive inotropic and chronotropic effects, but these effects were inhibited by pretreatments with ruthenium red (1.0 μM), capsazepine (10 μM), human calcitonin-gene-related peptide (CGRP8-37) (1.0 μM) and sensory neuron denervation, respectively. Based on these findings, we suggest that CGRP may be released by GLNVA from cardiovascular sensory neuron, and it then activates CGRP receptors on the coronary artery and atrium. The GLNVA-induced vasorelaxant effect in the vascular smooth muscle of the aorta is due to CGRP release associated K+ channel opening, and this effect eliminates capsaicin-derived excitability-associated K+ channel blocking activities.",
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Glyceryl nonivamide : A capsaicin derivative with cardiac calcitonin gene-related peptide releasing, K+ channel opening and vasorelaxant properties. / Lo, Yi Ching; Wu, Jiunn Ren; Wu, Sheng-Nan; Chen, Ing Jun.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 281, No. 1, 24.05.1997, p. 253-260.

Research output: Contribution to journalArticle

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