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

Calcitonin gene-related peptide (CGRP) has recently been demonstrated in sensory neurons of the eye. The purpose of the present study was to determine the effects of exogenous CGRP in the rabbit and cat eye. CGRP was injected intracamerally and the intraocular pressure was measured in cannulated eyes. The pupil diameter and the aqueous humor protein concentration were also measured. Indomethacin was used to prevent prostaglandin synthesis and tetrodotoxin (TTX) to block nerve conductance. In the rabbit eye, CGRP caused iridial hyperemia, a breakdown of the blood-aqueous barrier and increased intraocular pressure. These responses were dose-related. The increase in IOP as well as the breakdown of the blood-aqueous barrier could not be blocked with TTX or indomethacin. In cats CGRP caused a decrease in IOP and had only slight effect on the aqueous humor protein concentration. Neither in rabbits nor in cats had CGRP any detectable effect on the pupil size. Intracameral injection of 0.1 microgram (7.4 x 10(-11) moles) substance P together with 0.1 microgram (2.6 x 10(-11) moles) CGRP in rabbits caused maximal miosis but did not potentiate the intraocular effects of CGRP only. These results indicate that CGRP has marked vascular effects in the rabbit eye, causing a breakdown of the blood-aqueous barrier and increased IOP. The mechanism of this phenomenon does not involve prostaglandins neither nerve conduction, implying most likely a direct effect on the vascular smooth muscle. The mechanism of the decrease of IOP in cats remains unknown.
 ...
PMID:Effects of calcitonin gene-related peptide in the eye. A study in rabbits and cats. 326 93

The intraocular effects of substance P (SP) were studied in rabbits by measuring the pupil diameter, intraocular pressure (IOP), and aqueous humor protein concentration. Most of the animals were pretreated with indomethacin to avoid any interaction with prostaglandins. Intracameral injection of 1 to 150 ng of SP caused strong and persistent miosis without appreciably affecting the aqueous humor protein concentration or IOP. Intracameral injection of 0.8 to 11 micrograms of SP also induced an increase in IOP (7 to 8 mm Hg) without any apparent concomitant disruption in the blood-aqueous barrier. Outflow facility of aqueous humor decreased by a mean value of 50% after intracameral injection of 0.8 to 1.5 microgram of SP. Since the increase in IOP could be prevented by iridectomy, it was probably caused by a pupillary block from the intense miosis induced by SP. No disruption in the blood-aqueous barrier could be detected after intra-arterial infusion of 10 micrograms of SP or intravitreal injection of 100 ng of SP, indicating that the ciliary epithelium was practically insensitive to exogenous SP. Topical as well as subconjunctival administration of up to 1 mg of SP did not cause any irritative response in the eye. The results show that with concentrations of SP causing intense miosis, the eye does not exhibit visible hyperemia and disruption of the blood-aqueous barrier. This finding is consistent with the hypothesis that after certain irritative stimuli, miosis is mediated by a pathway separate from the hyperemia and disruption of the blood-aqueous barrier.
 ...
PMID:Intraocular effects of substance P in the rabbit. 616 Nov 2

A substance P analogue, (D-Pro2, D-Trp7,9)-SP, has been described to have SP antagonistic and SP agonistic effects in different tissues. We have investigated the effects of (D-Pro2, D-Trp7,9)-SP on the sphincter pupillae muscle, the blood aqueous barrier (BAB) and the intraocular pressure (IOP) in the albino rabbit eye. We also investigated the modifying effects of (D-Pro2, D-Trp7,9)-SP on miosis, BAB damage and IOP rise caused by SP, prostaglandin E1 (PGE1), capsaicin and on the miosis caused by electrical intracranial antidromic trigeminal nerve stimulation (NV stim). Endogenous PG synthesis was inhibited by systemic indomethacin i.v., cholinergic influence on the pupil size was inhibited with biperiden, i.v., adrenergic nerve influence by cervical sympathectomy just prior to the expts. Tubocurarine chloride was used to cause relaxation of striated muscles in the expts with NV stim. We found 100 micrograms (D-Pro2, D-Trp7,9)-SP to cause miosis, breakdown of the BAB with heavy leakage of Evans blue into the ciliary processes and aqueous humor, and a rise in IOP. At 10 micrograms (D-Pro2, D-Trp7,9)-SP caused slight miosis and did not inhibit the miosis caused by SP or capsaicin, but caused a significant reduction of the miotic response caused by PGE1 and NV stim. The rise in protein concentration in the aqueous humor caused by SP or PGE1 was slightly but significantly lower after pretreatment with (D-Pro2, D-Trp7,9)-SP. Thus (D-Pro2, D-Trp7,9)-SP was found to act as a SP agonist on the sphincter pupillae muscle, on the BAB and IOP. However, (D-Pro2, D-Trp7,9)-SP seemed to have some SP antagonistic effects on mechanisms that require sensory nerve conduction e.g. miosis caused by PGE1 and NV stim. The antagonistic mechanism is not clear. The SP analogue may have an unspecific membrane stabilizing effect or a toxic effect or block SP receptors on the sensory nerve fibers. Such effects of (D-Pro2, D-Trp7,9)-SP may explain also why the rise in protein concentration in the aqueous humor caused by SP and PGE1 was lower in eyes pretreated with (D-Pro2, D-Trp7,9)-SP.
 ...
PMID:In the eye (D-Pro2, D-Trp7,9)-SP is a substance P agonist, which modifies the responses to substance P, prostaglandin E1 and antidromic trigeminal nerve stimulation. 619 Mar 53

The present investigation was designed to evaluate the effect of selected peptides on pupillary diameter and intraocular pressure (IOP) in rabbits. Intracameral (IC) administration of neurotensin (NT) in doses of 5-100 micrograms produced a significant, long lasting and dose-dependent decrease in pupillary diameter without affecting IOP. NT-induced miosis appears to be relatively specific because a variety of peptides including Gn-RH, somatostatin, met-enkephalin, bombesin, leu-enkephalin or NT1-6, (a biologically inactive N-terminal fragment of NT), produced no effect on pupillary diameter; only substance P produced miosis similar to NT when tested in a dose equimolar to 30 micrograms of NT. In addition, peripheral (intravenous) administration of NT (100 micrograms/kg) was equally ineffective. Inhibition of prostaglandin synthesis with indomethacin, did not prevent subsequent NT-induced miosis. Finally, IC administration of an effective dose of NT (30 micrograms) did not alter the protein concentration in the aqueous humor. These results indicate that NT-induced miosis is not mediated by endogenous prostaglandins and that this effect of NT does not appear to involve disruption of the blood-aqueous barrier, suggesting that NT may play a role in regulation of pupillary diameter.
 ...
PMID:Intracameral administration of neurotensin induces miosis in the rabbit. 619 87

The effects of intracameral injections of CGRP(8-37) and CGRP(32-37) on pupil diameter and blood-aqueous barrier have been investigated in rabbits. The rabbits, which were pretreated with indomethacin and a muscarinic antagonist (biperiden), responded with miosis to both CGRP fragments. CGRP(8-37) was much more potent than CGRP(32-37) but one order of magnitude less potent than substance P. Nerve blockade with tetrodotoxin did not affect the response, indicating a direct effect on the iris sphincter muscle. Pre-treatment with the unselective tachykinin receptor antagonist spantide or the NK1 receptor selective antagonist GR82334 caused a rightward shift of the dose-response curves for both fragments, while the CCK receptor antagonist loxiglumide had no inhibitory effect. Neither of the fragments induced any marked leakage of Evans blue into the aqueous humor indicating that there was no agonistic interaction with CGRP receptors in the eye. We conclude that CGRP(8-37) and CGRP(32-37) are miotic agents in the rabbit eye, possibly by acting as neurokinin receptor agonists.
 ...
PMID:CGRP(8-37) and CGRP(32-37) contract the iris sphincter in the rabbit eye: antagonism by spantide and GR82334. 750 35

Degradation of substance P was studied in dog and rabbit aqueous humor. Substance P inactivation was followed by the bioassay using the isolated guinea pig ileum. Both rabbit and dog aqueous humor inactivated substance P. Rabbit aqueous humor inactivated the peptide faster than dog aqueous humor. Inactivation of substance P by rabbit aqueous humor was inhibited by diisopropylfluorophosphate while other enzyme inhibitors tested (captopril, phosphoramidon, mersalyl acid and p-chloromercuriphenyl-sulphonate) were practically ineffective or had a partial inhibitory effect. Our results suggest that serine proteases, rather than other peptidases, play a major role in the inactivation of substance P in aqueous humor.
 ...
PMID:Substance P inactivation by aqueous humor. 750 69

Ag presentation via the anterior chamber of the eye results in a form of immune deviation termed anterior chamber-associated immune deviation (ACAID). The hallmarks of this response are the suppression of delayed-type hypersensitivity with simultaneous induction of Ab production. In this study, we examined the role of the neuropeptides vasoactive intestinal peptide (VIP) and substance P (SP) and found that the levels of these two peptides are controlled by neurogenic stimulation of the eye by light, and that these molecules determine the outcome of Ag presentation in the eye. Mice reared under diurnal conditions had VIP in the iris and ciliary body (not free in aqueous humor) and low levels of SP. Mice that were reared in the dark (or dark-adapted) did not contain detectable levels of VIP but had high levels of SP. The adaptation of diurnal mice to the dark eliminated VIP and increased SP, while adapting dark-reared mice to the diurnal cycle increased VIP and reduced SP. We then tested the hypothesis that immune reactions resulting from Ag presentation in the eye were linked to SP and VIP. We found that a VIP receptor antagonist, when injected into the eye with Ag, reversed ACAID in diurnal mice, while a SP receptor antagonist restored ACAID to dark-adapted mice. We further determined that injection of Ag or TNF-alpha induced VIP release, while SP was liberated into the aqueous humor following reexposure of dark-reared mice to light. Our results demonstrate a close linkage of intraocular immune reactions to neuropeptide levels in the eye.
 ...
PMID:Neuropeptides modulate immune deviation induced via the anterior chamber of the eye. 754 31

Substance P immunoreactivity was measured by radioimmunoassay in aqueous humor samples of patients treated 13 h earlier with gentamicin, indomethacin or timolol. The indomethacin-treated group showed significantly decreased levels of substance P. The indomethacin effect is due to inhibition of the synthesis of arachidonic acid metabolites or involves non-specific mechanisms. It is suggested that suppression of substance P release may contribute to therapeutic effects of indomethacin in the human eye in conditions such as surgical miosis.
 ...
PMID:Indomethacin reduces substance P levels in human ocular aqueous humor. 768 3

The pathophysiological events leading to cellular proliferation in proliferative vitreoretinopathy are largely unknown. An involvement of neuropeptides in that disease has recently been discussed, as substance P was found to be highly enriched in the intraocular fluid of patients with proliferative vitreoretinopathy. In the present study, aqueous humor was analyzed for another neuropeptide, vasoactive intestinal polypeptide. Radioimmunoassay revealed significantly increased levels of that polypeptide in the aqueous humor of patients with proliferative vitreoretinopathy as compared with cataract patients who served as controls. As vasoactive intestinal polypeptide contributes to the environment of the retinal pigment epithelial cell layer and induces proliferation of these cells in vitro, this peptide may be involved in the pathogenetic mechanisms leading to cellular proliferation in proliferative vitreoretinopathy.
 ...
PMID:Different concentrations of vasoactive intestinal polypeptide in aqueous humor of patients with proliferative vitreoretinopathy and cataract patients. 780 11

Pituitary adenylate cyclase-activating peptide (PACAP)-like immunoreactivity was demonstrated by immunocytochemistry together with calcitonin gene-related peptide (CGRP)-like immunoreactivity in small to medium-sized neurons in the trigeminal ganglion and in nerve fibers in the iris, ciliary body, cornea, choroid and sclera of the rabbit eye. The regional distribution of PACAP-27- and PACAP-38-like immunoreactivity in the eye was studied by radioimmunoassay: the highest concentrations were found in the iris sphincter and ciliary body. The distribution pattern resembled that of CGRP-like immunoreactivity, which is a well-known constituent of sensory C-fibre neurons. Intravitreal injection of PACAP-27 or PACAP-38 induced conjunctival hyperemia, swelling of the anterior segment of the eye, miosis and breakdown of the blood-aqueous barrier, manifested as a marked aqueous flare response. Tetrodotoxin pretreatment inhibited the conjunctival hyperemia, the swelling of the anterior segment of the eye, and the miosis but not the aqueous flare response. The concentration of PACAP-like immunoreactivity in the aqueous humor was increased greatly following infrared irradiation of the iris, topical application of formaldehyde to the cornea, or intravitreal injection of endotoxin or bovine serum albumin. Also the concentration of CGRP-like immunoreactivity in the aqueous humor was increased greatly. Both in vivo and in vitro studies showed that capsaicin caused a parallel release of PACAP-like immunoreactivity and CGRP-like immunoreactivity from the uvea. Injection of PACAP-27 and PACAP-38 resulted in the release of CGRP-like immunoreactivity (and PACAP-like immunoreactivity) into the aqueous humor and PACAP-27 and PACAP-38 were also found to evoke tachykinin-mediated contractions of the isolated iris sphincter muscle, indicating that PACAP induces positive feedback on C-fibres. Thus, PACAP is a sensory neuropeptide in the eye. Since the PACAP-induced ocular responses mimicked the symptoms of inflammation, and since the PACAP-like immunoreactivity concentration in the aqueous humor was greatly increased following noxious stimulation, we suggest that it takes part in the inflammatory responses of the rabbit eye.
 ...
PMID:Distribution and effects of pituitary adenylate cyclase-activating peptide in the rabbit eye. 863 27


<< Previous 1 2 3 Next >>