Neuromediators and their receptors (adrenergic and endothelin types) in the eye.

The eye contains nerves that are derived from the central and peripheral nervous system. Every neurotransmitter or neuromediator of the brain is present in defined neurones of the retina which is also part of the central nervous system. Nerves innervating the iris, ciliary processes, cornea, choroid and parts of the eye other than the neuronal retina belong to the peripheral nervous system. These nerves contain catecholamines, acetylcholine and a variety of neuropeptides. The receptor-types shown to exist in the retina, iris, ciliary processes, cornea and other areas of the eye are numerous. In some instances the presence of specific types of receptors is associated with nerves containing the natural ligand while in other instances this is not the case e.g. for serotonin in the iris/ciliary processes. Thus certain receptor-types in the eye may be specifically controlled by hormones or mediators released locally from non-neuronal cells such as glial cells or retinal pigment epithelial cells. Evidence that noradrenaline has a functional role in the retina comes most convincingly from the finding that beta, alpha 1 and alpha 2-type receptors are present. Binding studies and agonist-induced effects on the secondary messengers cAMP and inositol phosphates show the beta receptors to be positively coupled to adenylate cyclases whereas alpha 2 receptors are negatively coupled to the enzyme. Stimulation of alpha 1 receptors triggers the production of inositol phosphates. A number of recent studies have shown that endothelin (ET) is an important vasoactive ocular peptide. We have focussed on determining the nature of ET receptors in the front of the eye. Autoradiographic studies have shown that specific 125I-ET-1 binding sites are associated with the iris, ciliary processes and corneal endothelium. The ETs stimulated inositol phosphates accumulation and decreased the synthesis of cAMP in the iris/ciliary processes. Thus is would appear that at least two types of ET receptors are present. Studies utilising the polymerase chain reaction provided evidence for the presence of ETB receptor subtype in the rabbit iris/ciliary body.