Effects of a chromogranin-derived peptide (CgA 47-66) in the writhing nociceptive response induced by acetic acid in rats.
Chromogranin A (CgA) is an acidic protein identified within a large variety of endocrine cells. Colocalized with catecholamines in chromaffin cells, CgA is a prohormone precursor of small biologically active peptides. Vasostatin (CgA 1-76) is the most conserved fragment of CgA and chromogranin A 47-66 peptide (CgA 47-66) possesses potent antimicrobial activities. The aim of this study was to test the hypothesis that CgA 47-66 may be involved in mechanisms modulating nociception. Thus, we used acetic acid (AA) which produces a delayed inflammatory response and episodes of abdominal writhing, a marker of pain, when injected intraperitoneally (i.p.) to rats. Administration (i.p.) of CgA 47-66 induced specific opposite dose-dependent effects depending on concentration. That is, CgA 47-66 below 0.5 mg/kg produced antinociceptive effects, whereas at 2 mg/kg it produced a marked pronociceptive effect. The latter effect was blocked by diltiazem and indomethacin. CgA 47-66-induced antinociceptive effects on AA-induced responses were reversed when the corticotropin-releasing factor (CRF) antagonist alpha-helical CRF 9-41 was i.p. injected to animals prior to AA and CgA 47-66 administration. The administration of i.p. calcitonin gene-related peptide (CGRP) or substance P (SP) evoked dose-dependent abdominal writhing; this effect was abolished when CgA 47-66 was injected. The present data suggest, for the first time, that a fragment of CgA, CgA 47-66, possesses potent antinociceptive effects at low doses. Although the mechanism triggered by this peptide is unknown, CRF receptors are likely to be involved.
Ghia
Jean-Eric
JE
INSERM Unit 575, Hôpital Civil Pavillon Poincaré, 1 place de l'Hôpital, 67091 Strasbourg, France.
Crenner
Francis
F
Metz-Boutigue
Marie-Hélène
MH
Aunis
Dominique
D
Angel
Fabielle
F
D019342:Acetic Acid / Q000633:toxicity*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage; D002317:Cardiovascular Agents; D053379:Chromogranin A; D002864:Chromogranins / Q000008:administration & dosage*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage; D004110:Diltiazem; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000008:administration & dosage; D008297:Male; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D059408:Pain Management; D010446:Peptide Fragments / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D013373:Substance P / Q000008:administration & dosage
D002317:Cardiovascular Agents; D053379:Chromogranin A; D002864:Chromogranins; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; C437333:chromofungin; C064110:vasostatin I; D013373:Substance P; D003346:Corticotropin-Releasing Hormone; D004110:Diltiazem; D015740:Calcitonin Gene-Related Peptide; D019342:Acetic Acid; D007213:Indomethacin