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)

Some biochemical factors of the iris-ciliary body of the rabbit have been examined for effects induced by water-soluble marihuana-derived material (MDM). Adenylate cyclase activity and sensitivity to beta-adrenergic agonists were unchanged, as measured 4 hours after MDM administration in vivo. Magnesium-dependent and anion-sensitive, but not sodium-potassium, ATPase activities were inhibited 6 hours after MDM administration in vivo, although they were unaffected by in vitro incubation. Topical administration of a potent substance P antagonist had no effect on the time course or magnitude of intravenous MDM-induced ocular effects in rabbit. Intravenously administered sugars antagonized the effects of MDM on intraocular pressure. A variety of drugs which display a range of biochemical effects varying from beta-adrenergic receptor agonism, to alteration of glycoprotein residues were employed. None of the agents employed, ranging from cAMP modifiers to protein synthesis blockers, had any effect on the MDM-induced response. It is apparent that the mechanism underlying the ocular hypotensive effect of MDM does not reside in mediation through adenylate cyclase, ATPase or substance P, but rather through a mechanism mediated by terminal sugar moieties on the molecule. The data suggest that modification of the surface membrane glycoprotein residues on the ciliary epithelium can induce marked alterations in aqueous humor flow rate.
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PMID:Marihuana-derived material: biochemical studies of the ocular responses. 316 May 44

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.
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PMID:Effects of calcitonin gene-related peptide in the eye. A study in rabbits and cats. 326 93

The mechanism of the intraocular pressure (IOP) elevation commonly seen in patients following neodymium (Nd):YAG laser posterior capsulotomy is unclear. Substance P, a potent polypeptide that is released into the eye after trigeminal nerve stimulation, may be the cause. In rabbits, topical application of nitrogen mustard causes a rise in IOP which is blocked by capsaicin, a presumed substance P depletor. In the present study, six eyes of three cynomolgus monkeys underwent extracapsular lensectomies. After 2 to 3 months, capsaicin was administered by retrobulbar injection on one side of each animal, and vehicle on the contralateral side. One day later, Nd:YAG laser posterior capsulotomies were performed using 31 mJ (total energy) per eye. Diurnal IOP measurements were made before and after the retrobulbar injections and the capsulotomies. Ten weeks later, laser capsulotomies were repeated using 200 mJ/eye without pretreatment with any potential blockers. None of the six eyes, each undergoing two separate capsulotomies 10 weeks apart, showed a postoperative rise in IOP. These results demonstrate that the cynomolgus monkey is a poor model for studying IOP elevation that often occurs following Nd:YAG laser posterior capsulotomy.
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PMID:Nd:YAG laser posterior capsulotomy does not produce elevation of intraocular pressure in cynomolgus monkeys. 341 75

Calcitonin gene-related polypeptide (CGRP) has been localised immunochemically within the rat and guinea pig anterior uvea to nerve fibres of trigeminal origin. As with substance P (1-3) the level of CGRP in the iris-ciliary body is depleted after thermal damage to the Gasserian ganglion and elevated in chronically sympathectically denervated eyes. Unlike substance P, a potent pupillary constrictor (4,5), CGRP has no notable miotic action, but does, however, cause an elevation of the intraocular pressure (IOP) accompanied by disruption of the blood-aqueous barrier. It is proposed that the diverse actions of these two sensory neuropeptides conjointly mediate the antidromic ocular injury response.
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PMID:Calcitonin gene-related polypeptide as a mediator of the neurogenic ocular injury response. 388 Apr 99

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.
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PMID:Intraocular effects of substance P in the rabbit. 616 Nov 2

The role of nerve conduction was studied in acute experimental uveitis caused by antidromic trigeminal nerve stimulation, prostaglandin E1 and E2 (PGE1 and PGE2), capsaicin and substance P (SP). Systemic indomethacin was used to prevent formation of endogenous prostaglandins, and intracameral injection of tetrodotoxin (TTX) was used to block nerve conduction. 10 micrograms TTX prevented the miosis and reduced the rise in intraocular pressure (IOP) usually caused by antidromic trigeminal nerve stimulation. At a low dose of PGE1 the IOP rise was blocked by TTX. At higher doses of PGE1 and PGE2 the pressure effect was not blocked by TTX; the miotic effect was markedly diminished. Capsaicin caused a rise in IOP that was almost totally blocked by TTX, while the miosis at high doses seemed unaffected. At low doses, capsaicin-induced miosis could be abolished by TTX. SP caused miosis in TTX treated eyes similar to that in untreated eyes; the IOP rise was delayed by TTX. The results indicate that nerve conduction plays a role in the IOP reaction caused by low doses of PGE1 and by capsaicin and SP. The mechanism suggested is an axon reflex, elicited in the anterior uvea and resulting in transmitter release in the ciliary processes. Nerve conduction with release of SP or a similar substance in the iris seems to be required for the miotic effects of PGE1 and PGE2. SP and capsaicin are similar in not requiring nerve conduction to cause miosis, but the capsaicin effect probably requires presence of nerves, since denervated eyes--which respond to SP--have been reported no to respond to capsaicin does similar to those used here.
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PMID:Ocular responses to antidromic trigeminal stimulation, intracameral prostaglandin E1 and E2, capsaicin and substance P. 617 Feb 10

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.
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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.
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PMID:Intracameral administration of neurotensin induces miosis in the rabbit. 619 87

The effects of the substance P analogue (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-SP on the ocular inflammatory responses (miosis, vasodilation, protein leakage into the aqueous humour and eye pressure rise) to antidromic trigeminal nerve stimulation (trigeminal stimulation), intracameral injections of substance P (SP), capsaicin, prostaglandin E1 (PGE1), compound 48/80 and histamine were investigated in albino rabbits. The effects of nerve blockade with tetrodotoxin and blockade of histamine receptors on the responses to compound 48/80 and histamine were also investigated. Histamine H1 receptors were blocked with clemastin and H2 receptors with cimetidin. Formation of endogenous prostaglandins was prevented with indomethacin. The pupil size and the eye pressure were measured. The aqueous humour was collected immediately after the animal was killed, and analyzed for protein concentration. (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-SP had no significant miotic effect, but tended to cause a break-down of the blood-aqueous barrier. Miosis caused by SP, trigeminal stimulation, capsaicin, PGE1, compound 48/80 or histamine was blocked by (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-SP. Histamine miosis was significantly reduced by blockade of nerve conduction or histamine receptors, while miosis caused by compound 48/80 was not. Nerve blockade abolished the rise in intraocular pressure caused by compound 48/80. Our results indicate that (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-SP is a specific SP blocker in the sphincter pupillae muscle. They are strong evidence for the hypothesis that trigeminal stimulation and capsaicin cause miosis by release of SP or a related substance (SPLI), and it seems likely that the miosis caused by PGE1 and compound 48/80 is also caused by SPLI release. Histamine miosis is probably mediated both by SP receptors and histamine receptors in the pupillary sphincter muscle.
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PMID:Effects of the substance P antagonist, (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-SP on the miotic response to substance P, antidromic trigeminal nerve stimulation, capsaicin, prostaglandin E1, compound 48/80 and histamine. 620 97

Angiotensin converting enzyme (ACE) -inhibitors inhibit degradation of inflammatory mediators substance P (SP) and bradykinin, which may further stimulate the synthesis of prostaglandins. The resulting increase in inflammatory mediators in tissues is suggested to be the reason for the dry cough, involving sensory C-fiber activation, among patients receiving ACE-inhibitor therapy. In the present study, the effect of an ACE-inhibitor, captopril, on ocular irritative responses was studied in the rabbit. Intravenous captopril decreased markedly the blood pressure and the intraocular pressure (IOP) modestly. Topical neutral formaldehyde elicits an irritative response in the eye mediated through sensory neuropeptides SP and calcitonin gene-related peptide (CGRP). Following topical neutral formaldehyde, the increase in IOP and breakdown of the blood-aqueous barrier were inhibited by captopril, while miosis was not affected. Cyclic AMP (cAMP) content in the aqueous humour was increased by captopril, and this increase was inhibited by indomethacin. Following YAG-laser anterior capsulotomy, captopril inhibited the increase in IOP, breakdown of the blood-aqueous barrier and miosis. The present study demonstrates that use of short-term administration of captopril prior to sensory nerve stimulation or YAG laser anterior capsulotomy does not enhance the ocular responses to these stimuli in the rabbit. In the present study, captopril inhibited these responses, at least partly by decreasing the blood pressure.
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PMID:Effect of captopril on ocular irritative response to topical neutral formaldehyde and YAG-laser capsulotomy in the rabbit. 859 Feb 56


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