FUNCTIONAL CONSEQUENCES OF PREJUNCTIONAL RECEPTOR ACTIVATION OR BLOCKADE IN THE IRIS

The iris is innervated by nerves of the sympathetic, parasympathetic, and sensory nervous systems. The terminal nerve fibres are endowed wit h prejunctional receptors which modulate neurotransmitter release. Act ivation or blockade of prejunctional receptors by drugs may have an in fluence on iris smooth muscle tone. Several findings are in favour of the hypothesis that prejunctional receptors may be involved in regulat ion of iris smooth muscle tone and/or pathophysiological events. (i). Release of acetylcholine from parasympathetic nerves of guinea-pig iri s sphincter evoked by electrical stimulation is subject to autoinhibit ion via prejunctional M(2) muscarinic receptors, and the release can b e enhanced by M(2) selective antagonists such as methoctramine or gall amine. Concomitantly with the increased neurotransmitter release, the sphincter contraction is enhanced in the presence of M(2) antagonists, since the postjunctional muscarinic receptors (presumably Ms(3) or at least not M(2)) are not simultaneously blocked. Unlike the non-select ive blocker atropine, M(2) antagonists are not expected to cause mydri asis but rather miosis. (ii). Sensory nerves are involved in pathophys iological events following ocular irritation. Release of substance P a nd/or neurokinin A from sensory nerves of rabbit iris is followed by a non-adrenergic-non-cholinergic iris sphincter contraction (mediated b y NK1 and NK3 receptors) which can be used to estimate sensory neurotr ansmitter release. Exocytotic release of the sensory neurotransmitters is inhibited by activation of alpha(2B)-adrenoceptors and probably al so via putative prejunctional imidazoline receptors. Alpha-adrenocepto rs are stimulated by oxymetazoline and other imidazoline derivatives ( which are agonists at imidazoline receptors) leading to a reduction of sensory neurotransmitter release, as evident from a decrease in evoke d sphincter contraction. Imidazolines in eye drops may not only cause relief in ocular inflammation due to postjunctional vasoconstriction b ut also possibly due to a prejunctional effect, a reduction of sensory neurotransmitter release. Reinforcement of inflammation due to releas e of sensory neurotransmitters may thus be prevented.