Distribution and origin of calcitonin gene‐related peptide (CGRP) immunoreactivity in the sensory innervation of the mammalian eye

Abstract

The occurrence, distribution, and origin of immunoreactive calcitonin gene-related peptide (CGRP) in nerves of rat, guinea pig, cat, and monkey eyes were investigated by immunocytochemistry, radioimmunoassay, and chromatography. A rich network of CGRP-immunoreactive nerve fibres was noted in the anterior uvea, which was widely distributed in both dilator and constrictor pupillae muscles and extended to the ciliary body and uveal blood vessels. Numerous CGRP-immunoreactive neuronal cells were present in the trigeminal ganglion. The extractable CGRP was 8.6 +/- 1.8 pmoles/gm of tissue in the iris and 44.0 +/- 8.1 pmoles/gm in the trigeminal ganglion. Following damage to the Gasserian ganglion a marked decrease of CGRP immunoreactivity was observed in the anterior uvea (control 11.3 +/- 1.6 pmoles/gm; operated 1.4 +/- 0.1 pmoles/gm) confirming the origin of the immunoreactive fibres from trigeminal primary sensory neurons. The sensory nature of the CGRP-immunoreactive fibres was substantiated by the depletion of CGRP immunoreactivity observed after treatment with capsaicin, which is known to cause selective degeneration of sensory neurons. Comparative studies on the distribution and colocalisation of CGRP and the putative sensory neurotransmitter substance P revealed a closely parallel distribution of the two peptides in certain regions of the uvea and their coexistence in a subpopulation of trigeminal primary sensory neurons. This study suggests that the sensory nervous system in the eye is more heterogeneous in terms of its putative neurotransmitters than previously indicated.

Nerve fibers in the urethral mucosa of canine penis are immunoreactive for both substance P and calcitonin gene-related peptide.

“…Furthermore, this study has confirmed the idea that substance P and CGRP were co-localized in a single neuron (GIBsoN et al, 1984;LEE et al, 1985;TERENGHI et al, 1985). No nerve fibers in the urethral epithelium were found to be immunoreactive for serotonin or other neuropeptides including VIP, NPY and Met-EK-8.…”

“…One predominant localization of CGRP neurons has been found in the sensory nerves, such as the small neurons in the trigeminal ganglion and in the spinal ganglia, as well as their terminals in the brain stem and spinal cord. Further immunohistochemical studies have reported the co-localization of CGRP and substance P in a single cell of the trigeminal ganglion and the dorsal root ganglia (GIBsoN et al, 1984;LEE et al, 1985;TERENGHI et al, 1985). These findings strongly suggest that CGRP is also involved in pain sensation.…”

Calcitonin gene‐related peptide (CGRP) is a potent non‐endothelium‐dependent inhibitor of coronary vasomotor tone

“…CGRP is widely distributed throughout the central and peripheral nervous systems in mammals (Springall et al, 1983;Terenghi et al, 1985) and there is evidence that CGRP in plasma is derived mainly from perivascular nerves (Zaidi et al, 1985).…”

Biology of Peptides From the Calcitonin Genes

“…The complex terminal branching pattern of these cells (Terenghi, Polak, Ghatei, Mulderry, Butler, Unger & Bloom, 1985) has been found to resemble that of cells containing tyrosine hydroxylase and differs from that of some other neuropeptides (Eldred & Karten, 1983). In the rat, cat, monkey and guinea-pig, CGRP-rich nerve fibres form a plexus over the iris, ciliary body, pupillary muscles, central area of the choroid (C-fibres) and the uveal and choroidal blood vessels (A6-fibres) in order of abundance (Terenghi et al 1985). .…”