In vitro study of the interaction of salmon calcitonin with mu, delta and kappa opioid agonists.
A possible interaction of salmon-calcitonin with opioid systems was studied in isolated tissues. Neurogenic contractions were elicited by electrical stimulation in guinea-pig ileum myenteric plexus-longitudinal muscle strips, rabbit vas deferens and mouse vas deferens. Bremazocine inhibited neurogenic contractions in all three tissues (presumably through kappa-receptors) [D-Pen2, D-Pen5]enkephalin and [Met5]enkephalin inhibited contractions in mouse vas deferens (presumably through delta-receptors), and [D-Ala2, N-Me-Phe4, Gly5-ol]enkephalin (DAMGO) inhibited contractions in guinea-pig ileum and mouse vas deferens (presumably through mu-receptors). All inhibitory effects were concentration-dependent. Salmon-calcitonin 0.1 IU/ml increased the effect of bremazocine in guinea-pig ileum and rabbit vas deferens and also increased the effects of [D-Pen2, D-Pen5]enkephalin and [Met5]enkephalin in mouse vas deferens. In contrast, salmon-calcitonin up to 0.4 IU/ml did not change the effect of bremazocine in mouse vas deferens and the effect of DAMGO in guinea-pig ileum and mouse vas deferens. It is concluded that salmon-calcitonin enhances agonist effects at opioid kappa- and delta- but not at opioid mu-receptors. The level of this interaction remains to be elucidated. The interaction may be the basis of the analgesic effect of salmon-calcitonin in vivo.
Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
M I
MI
Martín
M J
MJ
Alfaro
C
C
Goicoechea
M I
MI
Colado
D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D002116:Calcitonin / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D004745:Enkephalins / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011817:Rabbits; D011957:Receptors, Opioid / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects
D001575:Benzomorphans; D004745:Enkephalins; D011957:Receptors, Opioid; C028815:salmon calcitonin; D002116:Calcitonin; C027248:bremazocine