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 segme nts were preincubated with H-3-norepinephrine, superfused and electric ally-stimulated in vitro to evoke the discharge of H-3-norepinephrine. The effects of prejunctional modulators on evoked H-3-norepinephrine overflow were evaluated. Results. Stimulation-evoked (but not spontane ous) H-3-norepinephrine release was inhibited by alpha2-adrenergic, mu scarinic, dopaminergic, neuropeptide Y, and prostaglandin agonists and was enhanced by angiotensin II. Agonist-induced effects on H-3-norepi nephrine overflow were blocked by selective antagonists, where availab le. Yohimbine and atropine alone enhanced H-3-norepinephrine output, s uggesting that prejunctional alpha2-adrenergic and muscarinic receptor s undergo tonic activation by endogenously released neurotransmitters. Conclusions. Human ocular sympathetic nerves express inhibitory alpha 2-adrenergic, muscarinic, dopaminergic, prostaglandin, and neuropeptid e Y receptors and facilitatory angiotensin II receptors that control t he impulse-evoked release of H-3-norepinephrine. These receptors may b e useful targets for pharmacologic manipulation of the adrenergic syst em in vivo.