Study of mechanisms of calcitonin analgesia in mice. Involvement of 5-HT3 receptors.
The analgesic effect of calcitonin when serotonin (5-HT) concentration is increased and the involvement of some 5-HT receptors were studied using the writhing test in mice. 5-hydroxytryptophan (5-HTP) administration increased both 5-HT levels in the central nervous system (CNS) and calcitonin analgesia. The 5-HT(1A) agonist (+/-)-8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT) diminished calcitonin analgesia, this effect being antagonised by the 5-HT(1A) antagonist (WAY 100, 135). As the stimulation of 5-HT(1A) autoreceptors reduces the turnover of 5-HT, the effect of 8-OH-DPAT on calcitonin analgesia may be attributed to this decrease. The 5-HT(2A-2C) agonist (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI) diminished calcitonin analgesia. A sub-analgesic dose of the 5-HT(2A) antagonist ketanserin failed to prevent this effect. The 5-HT(3) agonist (+/-)-2-methyl-5-hydroxytryptamine maleate (2-methyl-5-HT) potentiated calcitonin analgesia, whereas it was significantly reduced by the 5-HT(3) antagonist tropisetron. The effect of 2-methyl-5-HT on calcitonin analgesia was also reversed by tropisetron, This result suggests that the 5-HT(3) receptor may play an important role in the relationship between calcitonin and the serotonergic system. Tropisetron also reversed the analgesia induced by calcitonin plus 5-HTP corroborating importance of the 5-HT(3) receptors.
Ormazábal
M J
MJ
Dpto. Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, 28040, Madrid, Spain.
Goicoechea
C
C
Alfaro
M J
MJ
Sánchez
E
E
Martín
M I
MI
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002116:Calcitonin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D007215:Indophenol / Q000031:analogs & derivatives / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D000077526:Tropisetron
D000700:Analgesics; D007211:Indoles; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C113896:dimethoxy-4-indophenyl-2-aminopropane; D012701:Serotonin; D007215:Indophenol; D000077526:Tropisetron; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C045918:2-methyl-5-HT; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002116:Calcitonin; D007650:Ketanserin