Functional cDNA clones coding for three isoforms of the human prostaglandin E receptor EP, subtype have been isolated from kidney and uterus cDNA libraries. The three isoforms, designated hEP,_,, hEP,_,, and hEP,_,,,, have open reading frames corresponding to 390,388 and 365 amino acids, respectively. They differ only in the length and amino acid composition of their carboxy-terminal regions, beginning at position 360. The human EP, receptor has seven predicted transmembrane spanning domains and therefore belongs to the G-protein-coupled receptor family. The rank order of potency for prostaglandins and related analogs in competition for [3H]PGE, specific binding to membranes prepared from transfected COS cells was comparable for all three isoforms, and as predicted for the EP, receptor, with PGEz = PGE, >> PGF, = iloprost > PGD, >> U46619. In addition, the EP,-selective agonist MB28767 was a potent competing ligand with an IC, value of 0.3 nM, whereas the EP,-selective antagonist AH6909 gave IC,, values of 2-7 PM and the EP,-selective agonist butaprost was inactive. In summary, we have cloned three isoforms of the human EP, receptor having comparable ligand binding properties.

BackgroundIn adults, excess adiposity has been associated with low-grade, chronic inflammation and compromised bone health, but less is known about these linkages in children. The purpose of this study was to compare the circulating levels of inflammatory cytokines, adipokines, osteokines, and bone markers at rest and in response to plyometric exercise between obese and normal weight adolescent females.MethodsTen normal weight (BMI = 21.3 ± 2) and 10 obese (BMI = 32.9 ± 4), postmenarcheal females, aged 13–17 years, performed one bout of plyometric exercise (5 circuits; 120 jumps). Blood samples were taken at rest, 5 min, 1 h, and 24 h post-exercise. Tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), insulin, leptin, osteocalcin, carboxy-terminal telopeptide (CTX), sclerostin, and parathyroid hormone (PTH) were measured in serum.ResultsCytokines were not different between groups at rest or over time with IL-6 increasing (+31%; p = 0.04) 5 min post-exercise and TNF-α decreasing (-9%; p = 0.001) 1 h post-exercise. Insulin and leptin were higher in the obese compared to the normal weight females. In both groups, insulin significantly increased 5 min post-exercise but remained elevated 1 h post-exercise only in the obese group. Leptin did not change in response to exercise. Osteocalcin was lower in the obese group across time and increased (+12%; p = 0.02) 24 h post-exercise in both groups. CTX was similar between groups at rest and decreased (-24%; p < 0.001) 1 h post-exercise. Sclerostin was similar between groups at rest, but there was a significant interaction reflecting a significant increase (+29%; p = 0.04) 5 min post-exercise in the obese group and a non-significant decrease (-13%; p = 0.08) in normal weight controls. PTH increased 5 min post-exercise, dropped 1 h post-exercise to lower than pre-exercise, and returned to baseline 24 h post-exercise in both groups.ConclusionObese adolescent females from our study had no evidence of resting inflammation or differences in bone resorption but show blunted bone formation when compared to normal weight controls. The direction and temporal changes in inflammatory cytokines, adipokines, and bone turnover markers to exercise were similar in both groups, reflecting an overall bone anabolic response for most biomarkers, except sclerostin, which increased only in the obese females immediately post-exercise, suggesting a different systemic regulation of sclerostin depending on adiposity.

[251I-Tyr8]-substance P and [251I]-neurokinin A binding assays in conjunction with tachykinin-receptor selective agonists ([Sar9Met(02)"]substance P for NK, and [PAla8]neurokinin A (4-10) for NK2) and antagonists (CP-99,994 for NK, and SR48968 for NK2). 2 The presence of high affinity, G-protein-coupled NK, receptors in guinea-pig lung parenchymal membranes has been confirmed. The rank order of affinity for competing tachykinins was as predicted for an NK, receptor: substance P = [Sar9Met (02) 6 In summary, these data demonstrate that guinea-pig lung parenchyma and guinea-pig trachea express both NK, and NK2 receptors.

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Thirteen female adolescent soccer players (14.3 ± 1.3 years) participated in a cross-over, double-blind trial examining the effects of Greek yogurt (GY) consumption on bone biomarkers during 5 days of intense soccer training. The study took place over two intervention weeks, which consisted of a pre-training assessment day, 5 training days, and a post-training assessment day. Participants completed the GY condition and a carbohydrate isocaloric placebo control pudding condition (CHO) in random order, 4 weeks apart. Morning, fasted, resting blood samples were collected pre- and post-training in each condition. Total osteocalcin (tOC), undercarboxylated osteocalcin (unOC), C-terminal telopeptide of type 1 collagen (CTX), osteoprotegerin (OPG), and receptor activator nuclear factor kappa-β ligand (RANKL) were measured in serum. The results showed no effects for time (pre- to post-training) or condition, and no interaction for tOC, CTX, OPG, RANKL, and the OPG/RANKL ratio. A time-by-condition interaction (p = 0.011) was observed in unOC, reflecting a post-training decrease in the GY, but not the CHO condition (−26% vs. −3%, respectively). However, relative unOC (% of tOC) decreased post-training (−16%), with no differences between conditions. These findings suggest that short-term high-impact intense training had no direct catabolic impact on bone metabolism, with GY adding no benefit beyond that of the isocaloric CHO control pudding.