Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is usually said that axons and nerve terminals do not contain messenger RNA (mRNA) and that peptide transmitters are packaged in granules and transported towards the periphery of the neuron. However, several recent reports challenge this view by showing evidence of the existence of mRNA in axons. In the present study, we demonstrate the existence of mRNA coding for gamma-preprotachykinin-A in rabbit iris by Northern blot analysis and Southern blot analysis of the polymerase chain reaction (PCR)-amplified products. Interestingly, mRNA coding for gamma-preprotachykinin-A was detected also in aqueous humor from eyes exposed to injury (infrared irradiation of the iris or retrobulbar injection of the C-fibre excitant capsaicin), but not from contralateral eyes and normal eyes of untreated rabbits. Our results suggest that the mRNA coding for gamma-preprotachykinin-A occurs in C-fibres in the iris and that it is released into the aqueous humor together with tachykinins in response to C-fibre stimulation.
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PMID:Release of preprotachykinin-A mRNA from rabbit iris upon C-fibre stimulation. 885 Nov 79

Following electroconvulsive treatment (ECT) of rabbits, preprotachykinin-A (PPT-A) mRNA was detected by Southern blot analysis of polymerase chain reaction (PCR)-amplified products in the cerebrospinal fluid (CSF) and aqueous humor of the eye. In contrast, no PPT-A mRNA could be detected in samples from untreated animals. In addition, several neuropeptides (substance P, neuropeptide Y, cholecystokinin, calcitonin gene-related peptide and pituitary adenylate cyclase activating peptide) were released into the CSF (and aqueous humor) following ECT. The results suggest that PPT-A mRNA was released together with neuropeptides into the CSF and aqueous humor in response to ECT. Indeed, previous studies have suggested that neurons can release neuropeptide mRNAs and that neurons are capable of taking up and expressing foreign mRNA. If neuropeptide mRNA can be taken up and utilized by another neuronal population, it might explain instances when neurons display 'phenotypic switch', i.e. the transient expression of novel neuropeptides.
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PMID:Electroconvulsive treatment evokes release of preprotachykinin-A mRNA into the cerebrospinal fluid and ocular aqueous humor of rabbits. 917 89

The effects of tachykinins on prostaglandin E2 (PGE2)-induced intraocular inflammation were investigated. PGE2 (0.01% or 0.1%) instillation induced iridal hyperemia and protein leakage into the aqueous humor in rabbits, but caused minimal miosis. Intravitreally injected substance P (SP) or neurokinin A (NKA), on the other hand, did not induce protein leakage into the aqueous humor in normal rabbits, but they (SP 10 micrograms/eye or NKA 50 micrograms/eye) did induce long-lasting miosis. The miotic activity of SP was about fivefold stronger than that of NKA. Intravitreally injected SP (10 micrograms/eye) but not NKA (50 micrograms/eye) increased PGE2 concentration in the aqueous humor in normal rabbits. In addition, SP (10 micrograms/eye) or NKA (50 micrograms/eye) markedly enhanced protein leakage into the aqueous humor induced by PGE2 instillation. Pretreatment with indomethacin partially blocked the enhancing effect of SP on protein leakage, while it did not block that of NKA. These results suggest that SP or NKA may enhance intraocular inflammation in vivo. However, the mechanisms of these effects of SP and NKA may be different. The enhancing effect of SP in eye inflammation may be partially due to an increased turnover of arachidonic acid into PGE2 caused by activation of the enzyme cyclooxygenase.
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PMID:Tachykinins as enhancers of prostaglandin E2-induced intraocular inflammation. 979 90

A quantitative analysis of peptidergic nerve fibres located in the trabecular meshwork of the guinea pig has been performed. Our results confirm that this structure contains VIP-, NPY- and substance P-like immunoreactivity as major neurotransmitters. These findings were obtained using immunohistochemical techniques. For this purpose serial sections of the eye were stained by immunohistochemistry for each of three neurotransmitters and stained sections were analysed by quantitative image analysis. Our findings demonstrate that SP-positive, NPY-positive and VIP-positive nerve fibres occupy 11.2, 4.9 and 2.4%, respectively, of the observed area (expressed as conventional units, C.U.) in the trabecular meshwork of the guinea pig eye. It is relevant to emphasize that the area containing these three types of peptidergic nerve fibres appears to be large (18.5 +/- 6.6 C.U.) in proportion to the total observed area. The innervation of the drainage angle of the guinea pig eye has been well described by many authors. This is the first study to report quantitative measurements of three types of peptidergic nerve fibres identified and measured in this area. The presence of these three neurotransmitters in the trabecular meshwork of guinea pig eye suggests their possible participation in aqueous humor regulation.
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PMID:Distribution of peptidergic nerve fibres in the guinea pig trabecular meshwork. 1119 86

Intraocular pressure displays a distinct circadian rhythm in animals and humans, with an increase at night and a decrease during the daytime. In animals, the IOP rhythm has been reported to be synchronized by environmental light and to persist in constant darkness, demonstrating a circadian component controlled by an endogenous pacemaker. The structures involved in the rhythmic regulation of intraocular pressure include the suprachiasmatic nucleus, which controls the activity of sympathetic and parasympathetic ocular innervation. These effectors are responsible for controlling the production (beta-adrenergic system) and the outflow (alpha1-adrenergic, parasympathetic system, prostaglandin) of aqueous humor. The production of aqueous humor is under adrenergic control (alpha1- and beta-receptors). Many neuropeptides such as vasoactive intestinal peptide, substance P, and the atrial natriuretic peptide are also involved in the regulation of intraocular pressure. A better understanding of the circadian regulation of intraocular pressure is needed for an appropriate treatment of ocular hypertension and glaucoma.
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PMID:[The neuroanatomical and physiological bases of variations in intraocular pressure]. 1531 70

The physiological roles of the cornea are to conduct external light into the eye, focus it, together with the lens, onto the retina, and to provide rigidity to the entire eyeball. Good vision thus requires maintenance of the transparency and proper refractive shape of the cornea. Although the cornea appears to be a relatively static structure, dynamic processes operate within and around the cornea at the tissue, cell, and molecular level. In this article, I review the mechanisms responsible for maintenance of corneal homeostasis as well as the development of new modes of treatment for various corneal diseases. I. The static cornea: structure and physiological functions. The cornea is derived from ectoderm, so that it can be considered as transparent skin. It is devoid of blood vessels and manifests the highest sensitivity in the entire body. The surface of the cornea is covered by tear fluid, which serves both as a lubricant and as a conduit for regulatory molecules. The cornea is also supplied with oxygen and various nutrients by the aqueous humor and a loop vascular system in addition to tear fluid. The cornea interacts with its surrounding tissues directly as well as indirectly through tear fluid or aqueous humor, with such interactions playing an important role in the regulation of corneal structure and functions. The resident cells of the cornea-epithelial cells, fibroblasts (keratocytes), and endothelial cells--also engage in mutual interactions through network systems. These interactions as well as those with infiltrated cells and regulation by nerves contribute to the maintenance of the normal structure and functions of the cornea as well as to the repair of corneal injuries. II. The dynamic cornea: maintenance of structure and functions by network systems. Developments in laser and computer technology have allowed observation of the cells and collagen fibers within the cornea. Furthermore, progress in cell and molecular biology has allowed characterization of dynamic network systems-including cell-cell and cell-extracellular matrix interactions as well as cytokines and neural factors-that contribute to the maintenance of corneal transparency and shape. III. Disruption of network systems: persistent corneal epithelial defects and corneal ulcer. Selection of the appropriate treatment for pathologic lesions of the cornea and the accompanying decrease in visual acuity requires localization of the lesion with regard to the epithelium, stroma, or endothelium of the cornea. In certain instances, however, it is not possible to determine the cause of the problem within the cornea. In such cases, the cause of the pathologic lesion and the target for treatment may lie in the surrounding tissues or environment. For example, corneal epithelial wound healing may be delayed, leading to the development of persistent epithelial defects, as a result of disruption of intercellular junctions between epithelial cells, an abnormality of the corneal basement membrane, altered concentrations of various cytokines in tear fluid, a lowered corneal sensation, or allergic reactions in the lid conjunctiva. Loss of corneal epithelial barrier function can further allow inflammatory cytokines present in tear fluid, together with infiltrated cells, to activate keratocytes and elicit excessive degradation of collagen in the stroma, thereby giving rise to corneal ulcer. IV. Development of new drugs for corneal diseases. We have attempted to apply the results of basic scientific research to the development of new drugs for corneal diseases that remain difficult to treat. The process of authorization for new drugs from the Ministry of Health, Labor, and Welfare takes more than two decades, however. The path from the bench to clinical practice is thus a long one. 1. Development of eyedrops for treatment of persistent corneal epithelial defects. We demonstrated the clinical efficacy of fibronectin eyedrops for the treatment of persistent epithelial defects of the cornea. However, the possibility of blood-borne infections has interfered with the development of serum-derived fibronectin as a drug. An automated machine for the preparation of autologous fibronectin eyedrops has therefore recently been developed. Furthermore, in seeking an alternative to fibronectin eyedrops, we are investigating the effects of a peptide corresponding to the second cell-binding domain of fibronectin on corneal epithelial wound healing. Considering that urokinase-type plasminogen activator may be expressed at the site of corneal epithelial defects and facilitates epithelial migration, the potential clinical application of annexin V, which stimulates the secretion of urokinase-type plasminogen activator for the treatment of persistent corneal epithelial defects is also now under investigation in Japan. 2. Development of eyedrops for treatment of neurotrophic keratopathy. Substance P, a neurotransmitter, stimulates corneal epithelial migration in a synergistic manner with insulin-like growth factor (IGF)--1. We have shown that eyedrops containing both the substance P-derived peptide FGLM-amide and the IGF-1--derived peptide SSSR are effective for the treatment of persistent corneal epithelial defects in individuals with diabetic keratopathy or neurotrophic keratopathy, both of which are associated with a reduction in corneal sensation. 3. Development of drugs for corneal ulcer. Treatment of corneal infection with antibiotics does not necessarily halt the process of corneal ulceration, which is characterized by excessive degradation of stromal collagen, or resolve persistent corneal epithelial defects. In addition to eyedrops for the treatment of persistent corneal epithelial defects, we have therefore also been working on the development of new drugs for the treatment of corneal ulcer. To this end, we have established an experimental system in which corneal fibroblasts are cultured in a three-dimensional collagen gel. With this system, we have shown that triptolide and steroids inhibit collagen degradation by corneal fibroblasts. Triptolide or its derivatives are thus potential drugs for the treatment of corneal ulcer and would work by acting directly on corneal fibroblasts rather than by inhibiting the secreted enzymes(matrix metalloproteinases) responsible for collagen degradation.
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PMID:[The cornea: stasis and dynamics]. 1841 11

Extrinsic and intrinsic sources of the autonomic nervous system contribute to choroidal innervation, thus being responsible for the control of choroidal blood flow, aqueous humor production or intraocular pressure. Neuropeptides are involved in this autonomic control, and amongst those, alarin has been recently introduced. While alarin is present in intrinsic choroidal neurons, it is not clear if these are the only source of neuronal alarin in the choroid. Therefore, we here screened for the presence of alarin in human cranial autonomic ganglia, and also in rat, a species lacking intrinsic choroidal innervation. Cranial autonomic ganglia (i.e., ciliary, CIL; pterygopalatine, PPG; superior cervical, SCG; trigeminal ganglion, TRI) of human and rat were prepared for immunohistochemistry against murine and human alarin, respectively. Additionally, double staining experiments for alarin and choline acetyltransferase (ChAT), tyrosine hydroxilase (TH), substance P (SP) were performed in human and rat ganglia for unequivocal identification of ganglia. For documentation, confocal laser scanning microscopy was used, while quantitative RT-PCR was applied to confirm immunohistochemical data and to detect alarin mRNA expression. In humans, alarin-like immunoreactivity (alarin-LI) was detected in intrinsic neurons and nerve fibers of the choroidal stroma, but was lacking in CIL, PPG, SCG and TRI. In rat, alarin-LI was detected in only a minority of cranial autonomic ganglia (CIL: 3.5%; PPG: 0.4%; SCG: 1.9%; TRI: 1%). qRT-PCR confirmed the low expression level of alarin mRNA in rat ganglia. Since alarin-LI was absent in human cranial autonomic ganglia, and only present in few neurons of rat cranial autonomic ganglia, we consider it of low impact in extrinsic ocular innervation in those species. Nevertheless, it seems important for intrinsic choroidal innervation in humans, where it could serve as intrinsic choroidal marker.
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PMID:Alarin in cranial autonomic ganglia of human and rat. 2549 46


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