Radioligand binding analysis of receptor subtypes in two FP receptor preparations that exhibit different functional rank orders of potency in response to prostaglandins.
The rat colon and Swiss 3T3 cells have been proposed as FP receptor preparations. However, the rank orders of potency for contraction of the rat colon and Ca++ signaling in Swiss 3T3 cells were found to be disparate. Although both appeared to be FP receptor preparations in that PGF2 alpha and FP receptor selective analogs were the most potent agonists, the potency ranking for other PGs and their analogs differed markedly. This presented two alternative major hypotheses for interpreting these data: (1) Swiss 3T3 cells and the rat colon possess different FP receptor subtypes and (2) the rat colon contains a heterogeneous population of prostanoid receptors. To further characterize prostanoid receptor populations in these two preparations, radioligand binding studies were performed with 3H-PGE2 and 3H-17-phenyl-PGF2 alpha. The rank order of potency for inhibition of 3H-PGE2 binding in the rat colon was consistent with EP3 receptor pharmacology. Thus, MB 28767, sulprostone and PGE2 were potent inhibitors, whereas PGF2 alpha, PGD2 and other analogs were substantially less potent. The rank order of potency for inhibition of 3H-17-phenyl-PGF2 alpha binding in the rat colon was consistent with the presence of an FP receptor. Thus, the potency rank order for the natural PGs was PGF2 alpha > PGD2 > PGE2 and among the synthetic analogs only PGF2 alpha analogs were potent competitors. In Swiss 3T3 cells an identical rank order of potency for eliciting a Ca++ transient signal and inhibition of 3H-17-phenyl-PGF2 alpha binding was obtained.(ABSTRACT TRUNCATED AT 250 WORDS)
Woodward
D F
DF
Department of Biological Sciences, Allergan, Inc., Irvine, California, USA.
Fairbairn
C E
CE
Krauss
A H
AH
Lawrence
R A
RA
Protzman
C E
CE
D016475:3T3 Cells; D000818:Animals; D003106:Colon / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D011453:Prostaglandins / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011982:Receptors, Prostaglandin / Q000145:classification*
D011453:Prostaglandins; D011982:Receptors, Prostaglandin; C027042:17-phenylprostaglandin F2alpha; D015237:Dinoprost; D015232:Dinoprostone