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. 1984

A Mandahl, and A Bill

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.

UI MeSH Term Description Entries
D008297 Male Males
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D011458 Prostaglandins E (11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities. PGE
D011680 Pupil The aperture in the iris through which light passes. Pupils
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002211 Capsaicin An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS. 8-Methyl-N-Vanillyl-6-Nonenamide,Antiphlogistine Rub A-535 Capsaicin,Axsain,Capsaicine,Capsicum Farmaya,Capsidol,Capsin,Capzasin,Gelcen,Katrum,NGX-4010,Zacin,Zostrix,8 Methyl N Vanillyl 6 Nonenamide,NGX 4010,NGX4010
D003189 p-Methoxy-N-methylphenethylamine A potent mast cell degranulator. It is involved in histamine release. Agent 48-80,BW 48-80,Compound 48-80,Preparation 48-80,Agent 48 80,Agent 4880,BW 48 80,BW 4880,Compound 48 80,Compound 4880,Preparation 48 80,Preparation 4880,p Methoxy N methylphenethylamine
D005260 Female Females
D006634 Histamine H1 Antagonists Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood. Antihistamines, Classical,Antihistaminics, Classical,Antihistaminics, H1,Histamine H1 Antagonist,Histamine H1 Receptor Antagonist,Histamine H1 Receptor Antagonists,Histamine H1 Receptor Blockaders,Antagonists, Histamine H1,Antagonists, Histamine H1 Receptor,Antihistamines, Sedating,Blockaders, Histamine H1 Receptor,First Generation H1 Antagonists,H1 Receptor Blockaders,Histamine H1 Blockers,Receptor Blockaders, H1,Antagonist, Histamine H1,Classical Antihistamines,Classical Antihistaminics,H1 Antagonist, Histamine,H1 Antagonists, Histamine,H1 Antihistaminics,Sedating Antihistamines
D006635 Histamine H2 Antagonists Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. Their clinically most important action is the inhibition of acid secretion in the treatment of gastrointestinal ulcers. Smooth muscle may also be affected. Some drugs in this class have strong effects in the central nervous system, but these actions are not well understood. Antihistaminics, H2,H2 Receptor Blockader,Histamine H2 Antagonist,Histamine H2 Blocker,Histamine H2 Receptor Antagonist,Histamine H2 Receptor Antagonists,Histamine H2 Receptor Blockader,Histamine H2 Receptor Blockaders,Antagonists, Histamine H2,Blockaders, Histamine H2 Receptor,H2 Receptor Blockaders,Histamine H2 Blockers,Receptor Antagonists, Histamine H2,Receptor Blockaders, H2,Antagonist, Histamine H2,Blockader, H2 Receptor,Blockaders, H2 Receptor,Blocker, Histamine H2,Blockers, Histamine H2,H2 Antagonist, Histamine,H2 Antagonists, Histamine,H2 Antihistaminics,H2 Blocker, Histamine,H2 Blockers, Histamine,Receptor Blockader, H2

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A Mandahl, and A Bill
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