Endothelin ETB receptors inhibit articular nociception and priming induced by carrageenan in the rat knee-joint.
The participation of the endothelin system on nociception and priming induced by carrageenan in the knee-joint was investigated. Intra-articular (i.a.) carrageenan (300 microg) caused long-lasting nociceptive effects (i.e., increases in paw elevation time [PET]), which were potentiated by endothelin-1 (dual endothelin ETA/ETB receptor agonist) and inhibited by sarafotoxin S6c (endothelin ETB receptor agonist; both at 30 pmol, i.a., 24 h beforehand). Priming the naive joint with carrageenan augmented nociceptive responses to a second carrageenan challenge, 72 h later. Carrageenan-induced priming, but not nociception, was potentiated by local BQ-788 (10 nmol, i.a., 15 min before priming; endothelin ETB receptor antagonist; N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D-1-methoxycarbonyl-tryptophanil-D-norleucine), but BQ-123 (endothelin ETA receptor antagonist; cyclo [D-Asp-Pro-D-Val-Leu]) was ineffective. Sarafotoxin S6c markedly suppressed carrageenan-induced priming to nociception triggered by carrageenan, endothelin-1 or sarafotoxin S6c, and BQ-788 prevented this action. Thus, selective endothelin ETB receptor agonists inhibit carrageenan-induced nociception and priming in the naive joint. This priming effect of carrageenan to nociception evoked by subsequent inflammatory insults is limited by an endothelin ETB receptor-operated mechanism.
Department of Pharmacology, CCB, Universidade Federal de Santa Catarina, Florianópolis SC 88049-900, Brazil.
Josélia B
JB
Daher
Glória E P
GE
Souza
Pedro
P
D'Orléans-Juste
Giles A
GA
Rae
D000818:Animals; D002351:Carrageenan / Q000633:toxicity*; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology; D017746:Joint Capsule / Q000187:drug effects / Q000502:physiology*; D007719:Knee Joint / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010146:Pain / Q000139:chemically induced; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D010456:Peptides, Cyclic; D051381:Rats; D017208:Rats, Wistar; D044023:Receptor, Endothelin B / Q000819:agonists / Q000502:physiology*
D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044023:Receptor, Endothelin B; D002351:Carrageenan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)