Calcitonin reverts pertussis toxin blockade of the opioid analgesia in mice.
The aim of this paper is to study the influence of salmon calcitonin (SCT) on opioid analgesia when opioid transduction pathways are functionally uncoupled from Gi/o proteins by treatment with pertussis toxin (PTX). The antinociceptive effect of morphine and three selective opioid agonists, [D-Ala2,N-Me-Phe2,Gly5-ol]enkephalin (DAMGO) (OP(3-mu receptor agonist), [D-Pen2.5]-enkephalin (OP-1-delta receptor agonist) and trans-( +/- )-3,4-dichloro-N-methyl-N-[2-1(-pyrrolidinyl)-cyclohexyl]-benzene-acetam ide methane sulfonate (U-50, 488H) (OP1-kappareceptor agonist) was evaluated, using the tail flick test, in mice treated with PTX or with PTX and SCT. PTX blocked the antinociceptive effect of the opioids, being the antinociception similar in control animals and in mice treated with PTX and SCT. Thus, SCT prevents the effect of the blockade of Gi/o-proteins. From this it could be suggested that calcitonin activates alternative antinociceptive mechanisms that are not dependent on Gi/o-proteins.
Goicoechea
C
C
Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
Ormazábal
M J
MJ
Abalo
R
R
Alfaro
M J
MJ
Martín
M I
MI
D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid; D000818:Animals; D002116:Calcitonin / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019204:GTP-Binding Proteins / Q000187:drug effects*; D008297:Male; D051379:Mice; D009020:Morphine; D010146:Pain / Q000188:drug therapy; D037342:Pertussis Toxin; D011957:Receptors, Opioid / Q000187:drug effects*; D014475:Uncoupling Agents / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000037:antagonists & inhibitors*
D000700:Analgesics; D000701:Analgesics, Opioid; D011957:Receptors, Opioid; D014475:Uncoupling Agents; D010566:Virulence Factors, Bordetella; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine; C028815:salmon calcitonin; D002116:Calcitonin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins