['To characterize the adenosine receptor modulation of norepinephrine (NE) release from sympathetic neurons in the isolated rabbit iris/ciliary body.', 'Iris/ciliary bodies were isolated from New Zealand White rabbits and incubated in the presence of 3H-NE. Norepinephrine release was elicited by field stimulation with varied frequencies from 5 to 30 Hz. The effects of adenosinergic and alpha 2 adrenergic compounds on NE release were determined and compared.', 'At a stimulation frequency of 5 Hz, the addition of the adenosine A1 agonist CHA did not significantly alter 3H-NE release. However, in the presence of the alpha 2 adrenergic antagonist yohimbine, the addition of CHA produced a dose-related reduction in 3H-NE release. The EC50 for this reduction was 14 nM. At a stimulus frequency of 20 Hz, the addition of CHA alone (10(-6) M) produced a significant reduction in 3H-NE release of 41%. The EC50s for the adenosine A1 agonists CHA- and R-PIA-induced suppression of 3H-NE release at 20 Hz were 32 and 24 nM, respectively. The adenosine A2 agonist CV-1808 did not alter 3H-NE release at stimulation frequencies of 5 or 20 Hz. Pretreatment of tissues with the adenosine A1 antagonist CPT or pertussis toxin reversed the suppression of 3H-NE release induced by CHA. Comparison of the inhibitory responses of CHA to the alpha 2 adrenergic agonist UK-14,304 at stimulus frequencies of 5 to 30 Hz demonstrated that this adenosine A1 agonist was effective only in suppressing NE release at frequencies of 20 Hz or greater. In contrast, the alpha 2 adrenergic agonist UK-14,304 was most effective in reducing NE release at 5 Hz.'] Is response to prejunctional adenosine receptors dependent on stimulus frequency?