Prejunctional modulation of norepinephrine release in the human iris-ciliary body.

PURPOSE To characterize the prejunctional mechanisms that control the impulse-evoked release of norepinephrine in the isolated, superfused human iris-ciliary body. METHODS Human iris-ciliary body tissue segments were preincubated with 3H-norepinephrine, superfused and electrically-stimulated in vitro to evoke the discharge of 3H-norepinephrine. The effects of prejunctional modulators on evoked 3H-norepinephrine overflow were evaluated. RESULTS Stimulation-evoked (but not spontaneous) 3H-norepinephrine release was inhibited by alpha 2-adrenergic, muscarinic, dopaminergic, neuropeptide Y, and prostaglandin agonists and was enhanced by angiotensin II. Agonist-induced effects on 3H-norepinephrine overflow were blocked by selective antagonists, where available. Yohimbine and atropine alone enhanced 3H-norepinephrine output, suggesting that prejunctional alpha 2-adrenergic and muscarinic receptors undergo tonic activation by endogenously released neurotransmitters. CONCLUSIONS Human ocular sympathetic nerves express inhibitory alpha 2-adrenergic, muscarinic, dopaminergic, prostaglandin, and neuropeptide Y receptors and facilitatory angiotensin II receptors that control the impulse-evoked release of 3H-norepinephrine. These receptors may be useful targets for pharmacologic manipulation of the adrenergic system in vivo.