Interaction of BW A868C, a prostanoid DP-receptor antagonist, with two receptor subtypes in the rabbit isolated saphenous vein.
In isolated rings of rabbit saphenous vein (RbSV) pre-contracted with 40 mM KCl, Prostaglandin E2 (PGE2), BW245C (a DP-receptor agonist) and PGD2 caused concentration-dependent relaxations with mean potencies (EC50) of 0.5, 38 and 114 nM respectively. The DP-receptor antagonist, BW A868C, antagonized BW245C concentration-effect (E/[A]) curves, although the corresponding Schild plot had a slope less than unity and displayed a clear infection. Analysis of the data yielded two pKB estimates of 8.5 and 4.9, the higher estimate being consistent with antagonism at DP-receptors. The pA2 estimate of 5.1 obtained for BW A868C against PGE2 was not statistically different to the lower pKB of 4.9 obtained against BW245C, and is probably indicative of antagonism at the EP4-receptor. PGD2 mediated responses were also antagonized by BW A868C, however the resultant E/[A] curves were 'bell shaped' in nature. The weak EP4-receptor antagonist AH23848B, also antagonized BW245C and PGD2 responses, yielding pA2 estimates of 5.6 and 5.5 respectively. These results suggest that in the RbSV, BW245C and PGD2 are nonselective agonists mediating relaxations through DP- and EP4-receptors. BW A868C also displayed an affinity for DP-receptors in this preparation, in addition to a second receptor subtype, presumably the EP4-receptor.
Lydford
S J
SJ
Department of Pharmacology, Astra Charnwood, Loughborough, Leicestershire, England.
McKechnie
K C
KC
Leff
P
P
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006827:Hydantoins / Q000494:pharmacology*; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058309:Receptors, Prostaglandin E, EP4 Subtype; D012501:Saphenous Vein / Q000378:metabolism*
D000889:Anti-Arrhythmia Agents; D001713:Biphenyl Compounds; D006827:Hydantoins; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; C058848:BW A868C; D011189:Potassium Chloride; C030669:BW 245C; C046926:AH 23848; D015232:Dinoprostone; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor