Biomaterial Database

Prostaglandin effects on the contractility of bovine trabecular meshwork and ciliary muscle. 1997

A H Krauss, and M Wiederholt, and A Sturm, and D F Woodward

Allergan, Inc., Irvine, CA 92612, USA.

The ocular hypotensive activity of prostaglandins (PGs) has previously been demonstrated in various species including man. The underlying mechanism of action of prostanoids other than PGF2 alpha remains contentious. Because the trabecular meshwork and ciliary muscle are believed to have a role in the regulation of aqueous humor outflow, the aim of this study was to identify the PG-receptor subtypes present in these tissues using receptor-selective agonists. Contractions of isolated strips of bovine trabecular meshwork and ciliary muscle were recorded isometrically in continuously perfused tissue chambers. Contractile activity of PGs was determined relative to a maximally effective concentration of carbachol (1 microM) as a standard agonist. The following prostanoids were employed: PGF2 alpha, 17-phenyl PGF2 alpha (FP-receptor agonists), sulprostone (EP3 > EP1-agonist), AH13205 (EP2-agonist), 11-deoxy PGE1 (non-selective EP-agonist), and U-46619 (TP-agonist). The thromboxane-mimetic U-46619 elicited a strong contraction of the trabecular meshwork with the highest concentration (1 microM) being almost twice as efficacious (186.6%) as the maximal carbachol concentration, whereas the effect on the ciliary muscle was small. The U-46619 induced trabecular meshwork contraction could be blocked with a potent and selective TP-receptor antagonist, 1 microM SQ29548, indicating the involvement of TP-receptors. The other PG-analogs studied had either no or a small but statistically significant effect. Thus, 17-phenyl PGF2 alpha (1 microM) weakly contracted the ciliary muscle (4.8%), sulprostone (1 microM) the trabecular meshwork (10.1%), 11-deoxy PGE1 (1 microM) and AH13205 (10 microM) elicited relaxations in both tissue precontracted with carbachol (1 microM). The relaxant effects were more pronounced in trabecular meshwork (15.6% for 11-deoxy PG1 and 21.4% for AH13205) than ciliary muscle (6.8 and 7.4% respectively). PGF2 alpha did not elicit a significant response in either tissue. Our studies suggest the existence of TP- and EP2-receptors in the bovine trabecular meshwork and potentially FP- and EP2-receptors in the ciliary muscle. In conclusion, thromboxane-mimetics and EP2-agonists have opposing activities on contractile elements in the meshwork and may modulate trabecular outflow in a functionally antagonistic manner. Prostanoid effects on ciliary muscle appear rather modest compared to parasympathomimetic drugs. It is conceivable that TP-agonists may substantially affect trabecular outflow.

UI	MeSH Term	Description	Entries
D009119	Muscle Contraction	A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.	Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009126	Muscle Relaxation	That phase of a muscle twitch during which a muscle returns to a resting position.	Muscle Relaxations,Relaxation, Muscle,Relaxations, Muscle
D011465	Prostaglandins, Synthetic	Compounds obtained by chemical synthesis that are analogs or derivatives of naturally occurring prostaglandins and that have similar activity.	PG Analog,PG Analogs,Prostaglandin Analog,Prostaglandin Analogs,Prostaglandin Analogue,Synthetic Prostaglandin,Prostaglandin Analogues,Synthetic Prostaglandins,Analog, PG,Analog, Prostaglandin,Analogs, PG,Analogs, Prostaglandin,Analogue, Prostaglandin,Analogues, Prostaglandin,Prostaglandin, Synthetic
D011982	Receptors, Prostaglandin	Cell surface receptors that bind prostaglandins with high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin receptor subtypes have been tentatively named according to their relative affinities for the endogenous prostaglandins. They include those which prefer prostaglandin D2 (DP receptors), prostaglandin E2 (EP1, EP2, and EP3 receptors), prostaglandin F2-alpha (FP receptors), and prostacyclin (IP receptors).	Prostaglandin Receptors,Prostaglandin Receptor,Receptor, Prostaglandin,Receptors, Prostaglandins,Prostaglandins Receptors
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D002924	Ciliary Body	A ring of tissue extending from the scleral spur to the ora serrata of the RETINA. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion.	Corpus Ciliare,Corpus Ciliaris,Bodies, Ciliary,Body, Ciliary,Ciliare, Corpus,Ciliares, Corpus,Ciliari, Corpus,Ciliaris, Corpus,Ciliary Bodies,Corpus Ciliares,Corpus Ciliari
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014129	Trabecular Meshwork	A porelike structure surrounding the entire circumference of the anterior chamber through which aqueous humor circulates to the SCHLEMM'S CANAL.	Meshwork, Trabecular,Meshworks, Trabecular,Trabecular Meshworks
D018078	Receptors, Prostaglandin E	Cell surface receptors which bind prostaglandins with a high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin E receptors prefer prostaglandin E2 to other endogenous prostaglandins. They are subdivided into EP1, EP2, and EP3 types based on their effects and their pharmacology.	PGE Receptors,PGE2 Receptors,Prostaglandin E Receptors,PGE Receptor,Prostaglandin E Receptor,E Receptor, Prostaglandin,E Receptors, Prostaglandin,Receptor, Prostaglandin E