The involvement of K+ channels and Gi/o protein in the antinociceptive action of the gallic acid ethyl ester.
The anti-hyperalgesic action, antinociception, and also the possible mechanisms involved in the action of gallic acid ethyl ester (GAEE) isolated from the aerial part of Phyllanthus urinaria, have been investigated in different models of chemical, mechanical and thermal nociception in mice and rats. GAEE given by intraperitoneal (i.p.), oral (p.o.), intrathecal (i.t.) or by intracerebroventricular (i.c.v.) routes produced dose-related antinociception when assessed against chemical nociception in mice. GAEE significantly inhibited the hyperalgesia induced by bradykinin or substance P in rat paw, but did not affect the hyperalgesia caused by carrageenan or prostaglandin E2. Furthermore, GAEE, in contrast to morphine, was completely ineffective in the hot-plate test in mice. The antinociception produced by GAEE (i.p.) in the formalin test was significantly reversed by i.c.v. treatment of animals with pertussis toxin and by i.t. administration of K+ channel blockers such as apamin, charybdotoxin or glibenclamide, but not by tetraethylammonium. In contrast, GAEE (i.p.) antinociception was unaffected by i.p. treatment of animals with naloxone or by nitric oxide precursor, L-arginine, and this action was not secondary to its anti-inflammatory effect, nor was it associated with non-specific effects such as muscle relaxation or sedation. Thus, GAEE produces dose-dependent and pronounced systemic, spinal and supraspinal antinociception in mice, probably via activation of K + channels and by a Gi/o pertussis toxin-sensitive mechanism.
Santos
A R
AR
Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
De Campos
R O
RO
Miguel
O G
OG
Cechinel-Filho
V
V
Yunes
R A
RA
Calixto
J B
JB
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005528:Foot / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D010147:Pain Measurement / Q000379:methods; D037342:Pertussis Toxin; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000633:toxicity; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000633:toxicity
D000700:Analgesics; D015221:Potassium Channels; D010566:Virulence Factors, Bordetella; D013373:Substance P; D005707:Gallic Acid; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D001920:Bradykinin