Individual variations of prostanoid agonist responses in XXXX aorta: evidence for the independent regulation of prostanoid receptor subtypes.

@entity2871 @entity1421 @entity2872 @entity95 @entity13078 @entity3774 @entity112
1 The frequency and selectivity of individual variations of prostanoid agonist responses in aortic strips from a population of male @entity95 was studied. Three levels of responsiveness to the @entity2871 mimetic @entity2872 occurred: responders (R), intermediate responders (IR), and non-responders (NR). R could be subdivided into R1 and R2 based on an enhanced potency of @entity3774 (PGF2 alpha) in R2. In the total population (n = 92), the phenotype frequency was: R, 69%; IR, 11%; and NR, 20%. In a subgroup of this population in which R1 and R2 phenotypes were determined (n = 63), the phenotype frequency was: R1, 54%; R2, 19%; IR, 6%; and NR, 21%. 2 The four @entity95 aorta phenotypes, R1, R2, IR, and NR, were characterized with respect to the rank orders of prostanoid agonist potency, agonist intrinsic activities, and the effects of the @entity2871 receptor antagonist @entity13078 . The rank order of prostanoid agonist potency was @entity2872 greater than PGF2 alpha greater than @entity1421 in R1 and R2, and PGF2 alpha greater than or equal to @entity1421 greater than @entity2872 in IR and NR. For each prostanoid agonist, the intrinsic activity was highest in R (R1 congruent to R2), intermediate in IR, and lowest in NR. In R1, @entity13078 inhibited all prostanoid agonist responses equally. The contractile effects of PGF2 alpha and @entity1421 were partially resistant to inhibition by @entity13078 in R2. Prostanoid agonist responses were not inhibited by @entity13078 in IR. 3 The potency of @entity112 was equivalent in R1, R2, IR, and NR. 4 It is concluded that there are individual variations in the functional expression of @entity2871 receptor sensitivity, i.e., prostanoid agonist responses inhibited by @entity13078 . Also, there are individual variations in the functional expression of the sensitivity of a non- @entity2871 receptor or receptors, i.e., prostanoid agonist responses not inhibited by @entity13078 . It has been proposed by others that prostanoid receptors be termed P-receptors and that the prostanoid agonist to which they are most sensitive be indicated by a preceding letter, e.g., TP- for @entity2871 receptor and FP- for PGF2 alpha-selective receptor. Accordingly, we proposed a working hypothesis that suggests the four phenotypes could result from the independent regulation of the functional expression of TP- and FP-receptor subtypes with (a) R2 containing both the TP- and FP-receptor subtypes in a fully functional state; (b) R1 containing only the functional TP-receptor; (c) IR containing only the functional FP-receptor; and (d) NR containing only a low efficacy FP-receptor system. 5 The mechanisms underlying the observed individual variations are unknown but could include changes in receptor number or affinity, changes in receptor-effector coupling, changes in a second messenger system, or changes in tissue degradative or uptake processes. Further study is needed to differentiate between these possibilities.
