Identification of the FP-receptor as a discrete entity by radioligand binding in biosystems that exhibit different functional rank orders of potency in response to prostanoids.
The definition of the FP-receptor is currently based on the functional potency of agonists. Functional studies suggest that the FP-receptor has particular sensitivity to PGF2 alpha and certain PGF2 alpha analogs but is also stimulated by PGD2 and PGE2. In order to examine the concept that these responses involve a single (FP) receptor, we compared functional responses with radioligand binding competition studies. In Swiss 3T3 cells, an identical potency rank order was obtained for Ca2+ transient signals and competition at binding sites for 3H-PGF2 alpha and 3H-17-phenyl PGF2 alpha (i.e., 17-phenyl PGF2 alpha > PGF2 alpha > PGD2 > PGE2), suggesting interaction at a single receptor. This conclusion was further supported by successive addition studies where cells pretreated with a maximally effective dose of PGF2 alpha were refractory to subsequent addition of PGF2 alpha, PGD2, or PGE2 but not PDGF. We also performed competition binding studies in the rat colon and uterus as representative tissues where the functional potency rank order is inconsistent with an FP receptor or any other prostanoid receptor subtype. Radioligand binding studies involving 3H-17-phenyl PGF2 alpha and 3H-PGE2 in the rat colon and uterus indicated the co-existence of both FP and EP3 receptors according to the competition afforded by natural PGs and selective analogs for FP and EP3 receptors. Thus, the FP-receptor can be identified in a mixed population of prostanoid receptors and this lends further support to the FP-receptor as a discrete entity.
Woodward
D F
DF
Department of Biological Sciences, Allergan, Inc., Irvine, CA 92713-9534, USA.
Fairbairn
C E
CE
Lawrence
R A
RA
D016475:3T3 Cells; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism; D005260:Female; D007700:Kinetics; D051379:Mice; D011453:Prostaglandins / Q000378:metabolism; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D011982:Receptors, Prostaglandin / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction; D014316:Tritium; D014599:Uterus / Q000378:metabolism
D011453:Prostaglandins; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D014316:Tritium; D015237:Dinoprost; D002118:Calcium