Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In human placental syncytiotrophoblast brush-border (BBM, facing the mother) and basal-plasma membranes (BPM, facing to fetus) we have recently demonstrated the presence of calcaemic hormone-specific receptors for parathyroid hormone and calcitonin, which could be implicated in calcium transport from the mother to the fetus. It is well recognized that signal transducing G proteins (guanosinc nucleotide-binding proteins) can associate with various transmembrane receptors and effector proteins, and regulate a variety of second-messenger systems and ion channels. In this present paper, we investigated the presence of a variety of alpha and beta subunits of G proteins in both syncytiotrophoblast, BBM and BPM by Western blot technique. For the first time, we were able to demonstrate the presence of G proteins in the bipolar syncytiotrophoblast membranes, which were evaluated by immunoblotting using affinity purified antiserum raised against the alpha subunits of Gi1, Gi1/i2, Gi3, G0, Gq, Gs, G7 and against the beta subunits. In BBM, we identified the alpha subunits of Gi1, Gi3, G0, Gq, Gs (42, 46 kDa), Gz and beta subunits. The same alpha subunits of G proteins were found in BPM, although alpha subunits of Gi1, Gq, Gs (46 kDa) were located predominantly in the BBM, and the alpha subunit of G0 was found preferentially in BPM. Moreover, in BBM and BPM, a purified antisera raised against the alpha subunits of Gi1 and Gs, detected a 105 kDa protein and a 67 kDa protein, respectively. Interestingly, the 67 kDa protein was preferentially located in BBM, and none of these proteins were detectable in membranes prepared from brain (control). The asymmetrical distribution of the alpha subunits of G proteins among the two different placental bipolar membranes might reflect the very specialized function of these syncytiotrophoblast membranes in ions and nutrients transport from the mother to the fetus.
 ...
PMID:Asymmetrical distribution of G proteins in syncytiotrophoblastic brush-border and basal-plasma membranes of human term placenta. 889 76

Resting Ca(2+) absorption by cortical thick ascending limbs (CALs) is passive and proceeds through the paracellular pathway. In contrast, parathyroid hormone (PTH) stimulates active, transcellular Ca(2+) absorption (J(Ca)). The Ca(2+)-sensing receptor (CaSR) is expressed on serosal membranes of CALs. In the present study, we tested the hypothesis that activation of the CAL CaSR indirectly inhibits passive Ca(2+) transport and directly suppresses PTH-induced cellular J(Ca). To test this theory, we measured J(Ca) and Na absorption (J(Na)) by single perfused mouse CALs. Net absorption was measured microfluorimetrically in samples collected from tubules perfused and bathed in symmetrical HEPES-buffered solutions or those in which luminal Na(+) was reduced from 150 to 50 mM. We first confirmed that Gd(3+) activated the CaSR by measuring intracellular Ca(2+) concentration ([Ca(2+)](i)) in CALs loaded with fura 2. On stepwise addition of Gd(3+) to the bath, [Ca(2+)](i) increased, with a half-maximal rise at 30 microM Gd(3+). J(Ca) and transepithelial voltage (V(e),) were measured in symmetrical Na(+)-containing solutions. PTH increased J(Ca) by 100%, and 30 microM Gd(3+) inhibited this effect. V(e) was unchanged by either PTH or Gd(3+). Similarly, NPS R-467, an organic CaSR agonist, inhibited PTH-stimulated J(Ca) without altering V(e). Neither PTH nor Gd(3+) affected J(Na). Addition of bumetanide to the luminal perfusate abolished J(Na) and V(e). These results show that CaSR activation directly inhibited PTH-induced transcellular J(Ca) and that cellular Ca(2+) and Na(+) transport can be dissociated. To test the effect of CaSR activation on passive paracellular Ca(2+) transport, J(Ca) was measured under asymmetrical Na conditions, in which passive Ca(2+) transport dominates transepithelial absorption. PTH stimulated J(Ca) by 24% and was suppressed by Gd(3+). In this setting, Gd(3+) reduced V(e) by 32%, indicating that CaSR activation inhibited both transcellular and paracellular Ca(2+) transport. We conclude that the CaSR regulates both active transcellular and passive paracellular Ca(2+) reabsorption but has no effect on J(Na) by CALs.
 ...
PMID:Calcium-sensing receptor regulation of PTH-dependent calcium absorption by mouse cortical ascending limbs. 1216 89