Further studies on ocular responses to DP receptor stimulation.
Prostaglandin D2 (PGD2) and the selective DP receptor agonist BW 245C have been previously shown to lower intraocular pressure in rabbits, while PGD2, but not BW 245C, caused plasma extravasation, eosinophil infiltration, and goblet cell depletion. In these present studies definition of the ocular pharmacology of prostaglandin D2 (PGD2) has been extended by using a further selective DP receptor agonist SQ 27986 and a potent and selective DP receptor antagonist BW A868C. In cats and rabbits SQ 27986 caused ocular hypotension. The ocular hypotensive effect of PGD2 in rabbits was blocked by pretreatment with the DP receptor antagonist BW A868C, whereas the activities of PGE2 and PGF2 alpha remained unaltered. The singular involvement of the DP receptor in changes in rabbit intraocular pressure evoked by PGD2 was thereby verified by using the antagonist BW A868C. In terms of effects on the ocular surface, SQ 27986 caused no increase in conjunctival microvascular permeability, no eosinophil infiltration, and no depletion of the goblet cell population. These findings reinforce the concept that selective DP receptor agonists may be useful for lowering intraocular pressure without causing ocular surface pathology. PGD2 induced increases in conjunctival microvascular permeability were inhibited by BW A868C, despite the fact that DP receptor agonists failed to evoke a plasma exudation response. This finding was unexpected and suggests a possible subdivision of the DP receptor designation.
Woodward
D F
DF
Department of Biological Sciences, Allergan, Inc., Irvine, CA 92713-9534.
Spada
C S
CS
Hawley
S B
SB
Williams
L S
LS
Protzman
C E
CE
Nieves
A L
AL
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002199:Capillary Permeability / Q000187:drug effects; D002415:Cats; D003228:Conjunctiva / Q000098:blood supply; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005123:Eye / Q000187:drug effects*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006827:Hydantoins / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D015230:Prostaglandin D2 / Q000494:pharmacology*; D011817:Rabbits; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin / Q000187:drug effects*
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006827:Hydantoins; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C058848:BW A868C; C066023:SQ 27986; D015237:Dinoprost; D015232:Dinoprostone; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor