Serotonergic mechanisms involved in calcitonin potentiation of kappa-opioid receptor-mediated effects on adrenal secretion.
Calcitonin can selectively modulate the effects of opioids on the rat hypothalamic-pituitary-adrenal axis and increase the release of corticosterone induced by a kappa-opioid receptor agonist. Considerable evidence supports the involvement of opioid and serotonergic systems in the analgesic effect of calcitonin. In this study, the involvement of hypothalamic serotonergic pathways in the calcitonin potentiation of the effect of (trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]-benzeneacetamide methane sulphonate (U-50,488H) on the secretion of corticosterone was examined. The correlation between the calcitonin-induced potentiation of the pituitary adrenal response to U-50,488H and changes in serotonin turnover was evaluated. Our results show that the increase in the release of corticosterone induced by treatment with calcitonin + U-50,488H was not evident when the turnover of serotonin was decreased by inhibition of its synthesis with m-hydroxybenzylhydrazine (NSD 1015) or by blockade of its metabolism with trans-2-phenylcyclopropylamine (tranylcypromine). Although other factors can not be discarded, from the present data it can be suggested that the serotonergic system plays an important role in the interaction calcitonin-kappa-opioid receptor agonist in the hypothalamic-pituitary-adrenal axis.
Ormazábal
M J
MJ
Departamento de Fisiología y Farmacología, Facultad de Medicina, Universidad de Murcia, Spain.
Milanés
M V
MV
Martín
M I
MI
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D006916:5-Hydroxytryptophan / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002116:Calcitonin / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D014191:Tranylcypromine / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004791:Enzyme Inhibitors; D006834:Hydrazines; D008996:Monoamine Oxidase Inhibitors; D017473:Receptors, Opioid, kappa; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D012701:Serotonin; D014191:Tranylcypromine; D006897:Hydroxyindoleacetic Acid; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D002116:Calcitonin; C004297:3-hydroxybenzylhydrazine; D006916:5-Hydroxytryptophan; D003345:Corticosterone