Abstract
AIMS—To study the distribution in the rat ciliary ganglion of neurons synthesising and storing the recently discovered neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) and neuronal nitric oxide synthase (NOS), the neuronal marker of the novel gaseous transmitter nitric oxide. METHODS—Neurons expressing PACAP and neuronal NOS mRNA were identified in the rat ciliary ganglion by in situ hybridisation with radiolabelled oligonucleotide probes. Immunocytochemistry was used to demonstrate immunoreactive neuropeptides and NOS. RESULTS—Immunocytochemistry demonstrated immunoreactivity for PACAP and NOS in a small number of neuronal cell bodies. In situ hybridisation revealed that NOS and PACAP were expressed in numerous ganglion cell somata. The well established ciliary messengers vasoactive intestinal peptide and neuropeptide Y were found in a large number of neuronal cell bodies. CONCLUSION—These results demonstrate that PACAP and NOS are synthesised and stored in the ciliary ganglion. These findings further illustrate the mixed nature of the ciliary ganglion and may provide a basis for the understanding of the diverse physiological functions of this ganglion.
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- Björklund H., Hökfelt T., Goldstein M., Terenius L., Olson L. Appearance of the noradrenergic markers tyrosine hydroxylase and neuropeptide Y in cholinergic nerves of the iris following sympathectomy. J Neurosci. 1985 Jun;5(6):1633–1640. doi: 10.1523/JNEUROSCI.05-06-01633.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bredt D. S., Hwang P. M., Glatt C. E., Lowenstein C., Reed R. R., Snyder S. H. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature. 1991 Jun 27;351(6329):714–718. doi: 10.1038/351714a0. [DOI] [PubMed] [Google Scholar]
- Dawson T. M., Bredt D. S., Fotuhi M., Hwang P. M., Snyder S. H. Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7797–7801. doi: 10.1073/pnas.88.17.7797. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haefliger I. O., Flammer J., Lüscher T. F. Heterogeneity of endothelium-dependent regulation in ophthalmic and ciliary arteries. Invest Ophthalmol Vis Sci. 1993 Apr;34(5):1722–1730. [PubMed] [Google Scholar]
- Haefliger I. O., Flammer J., Lüscher T. F. Nitric oxide and endothelin-1 are important regulators of human ophthalmic artery. Invest Ophthalmol Vis Sci. 1992 Jun;33(7):2340–2343. [PubMed] [Google Scholar]
- Hope B. T., Michael G. J., Knigge K. M., Vincent S. R. Neuronal NADPH diaphorase is a nitric oxide synthase. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2811–2814. doi: 10.1073/pnas.88.7.2811. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kuwayama Y., Grimes P. A., Ponte B., Stone R. A. Autonomic neurons supplying the rat eye and the intraorbital distribution of vasoactive intestinal polypeptide (VIP)-like immunoreactivity. Exp Eye Res. 1987 Jun;44(6):907–922. doi: 10.1016/s0014-4835(87)80053-2. [DOI] [PubMed] [Google Scholar]
- Landis S. C., Jackson P. C., Fredieu J. R., Thibault J. Catecholaminergic properties of cholinergic neurons and synapses in adult rat ciliary ganglion. J Neurosci. 1987 Nov;7(11):3574–3587. doi: 10.1523/JNEUROSCI.07-11-03574.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leblanc G. G., Landis S. C. Target specificity of neuropeptide Y-immunoreactive cranial parasympathetic neurons. J Neurosci. 1988 Jan;8(1):146–155. doi: 10.1523/JNEUROSCI.08-01-00146.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leblanc G. G., Trimmer B. A., Landis S. C. Neuropeptide Y-like immunoreactivity in rat cranial parasympathetic neurons: coexistence with vasoactive intestinal peptide and choline acetyltransferase. Proc Natl Acad Sci U S A. 1987 May;84(10):3511–3515. doi: 10.1073/pnas.84.10.3511. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li C. G., Rand M. J. Evidence that part of the NANC relaxant response of guinea-pig trachea to electrical field stimulation is mediated by nitric oxide. Br J Pharmacol. 1991 Jan;102(1):91–94. doi: 10.1111/j.1476-5381.1991.tb12137.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mann R. M., Riva C. E., Stone R. A., Barnes G. E., Cranstoun S. D. Nitric oxide and choroidal blood flow regulation. Invest Ophthalmol Vis Sci. 1995 Apr;36(5):925–930. [PubMed] [Google Scholar]
- Miyata A., Arimura A., Dahl R. R., Minamino N., Uehara A., Jiang L., Culler M. D., Coy D. H. Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun. 1989 Oct 16;164(1):567–574. doi: 10.1016/0006-291x(89)91757-9. [DOI] [PubMed] [Google Scholar]
- Moller K., Zhang Y. Z., Håkanson R., Luts A., Sjölund B., Uddman R., Sundler F. Pituitary adenylate cyclase activating peptide is a sensory neuropeptide: immunocytochemical and immunochemical evidence. Neuroscience. 1993 Dec;57(3):725–732. doi: 10.1016/0306-4522(93)90018-b. [DOI] [PubMed] [Google Scholar]
- Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
- Mulder H., Uddman R., Moller K., Elsås T., Ekblad E., Alumets J., Sundler F. Pituitary adenylate cyclase activating polypeptide is expressed in autonomic neurons. Regul Pept. 1995 Sep 22;59(1):121–128. doi: 10.1016/0167-0115(95)00082-m. [DOI] [PubMed] [Google Scholar]
- Mulder H., Uddman R., Moller K., Zhang Y. Z., Ekblad E., Alumets J., Sundler F. Pituitary adenylate cyclase activating polypeptide expression in sensory neurons. Neuroscience. 1994 Nov;63(1):307–312. doi: 10.1016/0306-4522(94)90025-6. [DOI] [PubMed] [Google Scholar]
- Myrsén U., Sundler F. Neuropeptide Y is expressed in islet somatostatin cells of the hamster pancreas: a combined immunocytochemical and in situ hybridization study. Regul Pept. 1995 May 4;57(1):65–76. doi: 10.1016/0167-0115(95)00020-c. [DOI] [PubMed] [Google Scholar]
- Nilsson S. F., Bill A. Vasoactive intestinal polypeptide (VIP): effects in the eye and on regional blood flows. Acta Physiol Scand. 1984 Aug;121(4):385–392. doi: 10.1111/j.1748-1716.1984.tb07470.x. [DOI] [PubMed] [Google Scholar]
- Nilsson S. F., De Neef P., Robberecht P., Christophe J. Characterization of ocular receptors for pituitary adenylate cyclase activating polypeptide (PACAP) and their coupling to adenylate cyclase. Exp Eye Res. 1994 Apr;58(4):459–467. doi: 10.1006/exer.1994.1039. [DOI] [PubMed] [Google Scholar]
- Nilsson S. F. Neuropeptide Y (NPY): a vasoconstrictor in the eye, brain and other tissues in the rabbit. Acta Physiol Scand. 1991 Apr;141(4):455–467. doi: 10.1111/j.1748-1716.1991.tb09106.x. [DOI] [PubMed] [Google Scholar]
- Nilsson S. F. PACAP-27 and PACAP-38: vascular effects in the eye and some other tissues in the rabbit. Eur J Pharmacol. 1994 Feb 21;253(1-2):17–25. doi: 10.1016/0014-2999(94)90752-8. [DOI] [PubMed] [Google Scholar]
- Stone R. A., McGlinn A. M., Kuwayama Y., Grimes P. A. Peptide immunoreactivity of the ciliary ganglion and its accessory cells in the rat. Brain Res. 1988 Dec 20;475(2):389–392. doi: 10.1016/0006-8993(88)90632-4. [DOI] [PubMed] [Google Scholar]
- Sun W., Erichsen J. T., May P. J. NADPH-diaphorase reactivity in ciliary ganglion neurons: a comparison of distributions in the pigeon, cat, and monkey. Vis Neurosci. 1994 Sep-Oct;11(5):1027–1031. doi: 10.1017/s0952523800003965. [DOI] [PubMed] [Google Scholar]
- Suzuki N., Hardebo J. E., Kåhrström J., Owman C. Neuropeptide Y co-exists with vasoactive intestinal polypeptide and acetylcholine in parasympathetic cerebrovascular nerves originating in the sphenopalatine, otic, and internal carotid ganglia of the rat. Neuroscience. 1990;36(2):507–519. doi: 10.1016/0306-4522(90)90001-7. [DOI] [PubMed] [Google Scholar]
- Terenghi G., Polak J. M., Allen J. M., Zhang S. Q., Unger W. G., Bloom S. R. Neuropeptide Y-immunoreactive nerves in the uvea of guinea pig and rat. Neurosci Lett. 1983 Nov 21;42(1):33–38. doi: 10.1016/0304-3940(83)90417-2. [DOI] [PubMed] [Google Scholar]
- Toda N., Kitamura Y., Okamura T. Functional role of nerve-derived nitric oxide in isolated dog ophthalmic arteries. Invest Ophthalmol Vis Sci. 1995 Mar;36(3):563–570. [PubMed] [Google Scholar]
- Tucker J. F., Brave S. R., Charalambous L., Hobbs A. J., Gibson A. L-NG-nitro arginine inhibits non-adrenergic, non-cholinergic relaxations of guinea-pig isolated tracheal smooth muscle. Br J Pharmacol. 1990 Aug;100(4):663–664. doi: 10.1111/j.1476-5381.1990.tb14072.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tyrrell S., Siegel R. E., Landis S. C. Tyrosine hydroxylase and neuropeptide Y are increased in ciliary ganglia of sympathectomized rats. Neuroscience. 1992;47(4):985–998. doi: 10.1016/0306-4522(92)90046-5. [DOI] [PubMed] [Google Scholar]
- Tøttrup A., Knudsen M. A., Gregersen H. The role of the L-arginine-nitric oxide pathway in relaxation of the opossum lower oesophageal sphincter. Br J Pharmacol. 1991 Sep;104(1):113–116. doi: 10.1111/j.1476-5381.1991.tb12393.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang Z. Y., Alm P., Håkanson R. Distribution and effects of pituitary adenylate cyclase-activating peptide in the rabbit eye. Neuroscience. 1995 Nov;69(1):297–308. doi: 10.1016/0306-4522(95)00258-k. [DOI] [PubMed] [Google Scholar]
- Wiencke A. K., Nilsson H., Nielsen P. J., Nyborg N. C. Nonadrenergic noncholinergic vasodilation in bovine ciliary artery involves CGRP and neurogenic nitric oxide. Invest Ophthalmol Vis Sci. 1994 Jul;35(8):3268–3277. [PubMed] [Google Scholar]
- Yamamoto R., Bredt D. S., Snyder S. H., Stone R. A. The localization of nitric oxide synthase in the rat eye and related cranial ganglia. Neuroscience. 1993 May;54(1):189–200. doi: 10.1016/0306-4522(93)90393-t. [DOI] [PubMed] [Google Scholar]
- Zhang Y. Z., Sjölund B., Moller K., Håkanson R., Sundler F. Pituitary adenylate cyclase activating peptide produces a marked and long-lasting depression of a C-fibre-evoked flexion reflex. Neuroscience. 1993 Dec;57(3):733–737. doi: 10.1016/0306-4522(93)90019-c. [DOI] [PubMed] [Google Scholar]