Effects of selective alpha 2-adrenoreceptor stimulation on capsaicin-evoked substance P release from primary cultured dorsal root ganglion neurons.Pharmazie. 2010 Mar; 65(3):202-5.P
Alpha2 adrenoreceptors are expressed in dorsal root ganglion (DRG) neurons and may be involved in inflammation or other physiological and pathophysiological conditions. To determine the effects of administration of selective alpha2 adrenoreceptor agonists or antagonists on substance P (SP) release from DRG neurons without or with capsaicin stimulation, primary cultured embryonic rat DRG neurons were preincubated with the selective alpha2 adrenoreceptor agonist clonidine (10(-5) mol/L) or the alpha2 adrenoreceptor antagonist yohimbine (10(-5) mol/L) for 4 days, respectively, followed by the addition of capsaicin (10(-7) nmol/L) for additional 10 min. Cultures were examined by radioimmunoassay (RIA) for detecting SP levels released from DRG neurons before and after capsaicin stimulation. Expression of SP mRNA and vanilloid receptor 1 (VR1) mRNA was determined by RT-PCR. Administration of the selective alpha2 adrenoreceptor agonist clonidine for 4 days could decrease capsaicin-evoked SP release but not basal SP release. Administration of clonidine could decrease VR1 mRNA expression but not SP mRNA. Administration of the selective alpha2 adrenoreceptor antagonist yohimbine did not have these effects. The inhibitory role of the selective alpha2 adrenoreceptor agonist clonidine on capsaicin-evoked SP release may be through decreasing VR1 mRNA levels then reducing the sensitivity of nociceptors to capsaicin. The data provided in the present study suggest that adrenergic modulation on primary sensory neurons by an alpha2 adrenoreceptor agonist may contribute to the analgesic effects in neurogenic inflammation.