Natural Diterpenes from Coffee, Cafestol, and Kahweol Induce Peripheral Antinoceception by Adrenergic System Interaction

摘要

Cafestol and kahweol are diterpenes found only in the non-saponified lipid fraction of coffee. They are released during boiling and retained in the filtration process. Previous studies have shown peripheral antinociception induced by endogenous opioid peptides released by these diterpenes. Considering that the activation of the opioid system leads to a noradrenaline release, the aim of this study was to verify the participation of the noradrenergic system in the peripheral antinociception induced by cafestol and kahweol. Hyperalgesia was induced by an intraplantar injection of prostaglandin E-2 (2 mu g). Cafestol or kahweol (80 mu g/paw) were administered locally into the right hindpaw alone, and after the agents alpha(2)-adrenoceptor antagonist yohimbine (5, 10 and 20 mu g/paw), alpha(2A)-adrenoceptor antagonist BRL 44408 (40 mu g/paw), alpha(2B)-adrenoceptor antagonist imiloxan (40 mu g/paw), alpha(2C)-adrenoceptor antagonist rauwolscine (10, 15 and 20 mu g/paw), alpha(2D)-adrenoceptor antagonist RX 821002 (40 mu g/paw), alpha(1)-adrenoceptor antagonist prazosin (0.5, 1 and 2 mu g/paw), or beta-adrenoceptor antagonist propranolol (150, 300 and 600 ng/paw), respectively. Noradrenaline reuptake inhibitor reboxetine (30 mu g/paw) was administered prior to cafestol or kahweol low dose (40 mu g/paw) and guanetidine 3 days prior to the experiment (30 mg/kg, once a day), depleting the noradrenaline storage. Intraplantar injection of cafestol or kahweol (80 mu g/paw) induced a peripheral antinociception against hyperalgesia induced by PGE(2). This effect was reversed by intraplantar injections of yohimbine, rauwolscine, prazosin and propranolol. Reboxetine injection intensified the antinociceptive effect of cafestol or kahweol low-dose, and guanethidine reversed almost 70% of the cafestol or kahweol-induced peripheral antinociception. This study gives evidence that the noradrenergic system participates in cafestol and kahweol-induced peripheral antinociception with the release of endogenous noradrenaline.