Thromboxane A2-mimetics are potent microvascular permeability factors in the conjunctiva.
These studies demonstrate that the thromboxane (Tx) A2 mimetics U-46619, U-44069 and carbocyclic-TxA2 elicit a microvascular permeability response in the conjunctiva. U-46619 and U-44069 are among the most potent microvascular permeability factors described to date for the conjunctiva; their potency is exceeded only by that reported for leukotrienes D4 and E4. The conjunctival microvascular permeability response to U-46619 was inhibited by the TxA2-antagonists daltroban (BM 13505) and SQ 29548. Prostaglandin (PG) D2 also increased conjunctival microvascular permeability, but was less potent than U-46619 and far less susceptible to pretreatment with daltroban or SQ 29548. PGE2, PGF2 alpha and the prostacyclin analog carbocyclin did not increase conjunctival microvascular permeability. It appears that the conjunctiva exhibits a unique microvascular permeability response to TxA2-mimetics: this view is experimentally supported by the absence of a cutaneous microvascular permeability response to U-46619, U-44069 and carbocyclic-TxA2.
Discovery Research, Allergan, Inc., Irvine, California.
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Woodward
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Nieves
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Williams
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002199:Capillary Permeability / Q000187:drug effects*; D003228:Conjunctiva / Q000098:blood supply*; D003231:Conjunctivitis / Q000209:etiology; D005231:Fatty Acids, Unsaturated; D006168:Guinea Pigs; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D015230:Prostaglandin D2 / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011450:Prostaglandin Endoperoxides, Synthetic; C024587:thromboxane A2, carbocyclic; C028429:U 44069; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D015230:Prostaglandin D2