Peripheral alpha-adrenoceptors are involved in mediating neurogenic inflammation. To characterize the effects of acute administration of selective alpha adrenoreceptor agonists or antagonists on capsaicin-evoked substance P (SP) release from dorsal root ganglion (DRG) neurons, dissociated cultured DRG neurons were preincubated with selective alpha 1-adrenoreceptor agonist phenylephrine (10(-5) mol/L), alpha 1-adrenoreceptor antagonist prazosin (10(-6) mol/L), alpha 2-adrenoreceptor agonist clonidine (10(-5) mol/L), alpha 2-adrenoreceptor antagonist yohimbine (10(-5) mol/L) for 10 min, followed by the addition of capsaicin (10(-7) nmol/L) for additional 10 min. Radioimmunoassay (RIA) was employed to determine if the capsaicin-evoked enhancement of neuropeptide release was subject to adrenergic modulation. Expression of SP mRNA was determined by RT-PCR. Acute exposure of selective alpha 1-adrenoreceptor agonist phenylephrine could increase capsaicin-evoked SP release from primary cultured DRG neurons. Expression of SP mRNA was not affected by acute stimulation with these adrenoreceptor agonists or antagonists. The data provided in the present study suggest that the excitatory effect of alpha 1-adrenoreceptor agonist on capsaicin-evoked release of neuropeptide from primary cultured DRG neurons is likely to be mediated by activation of VR1 to influence capsaicin sensitivity but not by promotion of SP synthesis under acute stimulative states.