Expression of the genes encoding the vasopressin-activated calcium-mobilizing receptor and the dual angiotensin II/vasopressin receptor in the rat central nervous system
- PMID: 10849213
- DOI: 10.1046/j.1365-2826.2000.00499.x
The distributions of two newly discovered receptors, the vasopressin-activated calcium-mobilizing receptor (VACM-1) and the dual angiotensin II/vasopressin receptor (AII/AVP), in the central nervous system (CNS) of the rat were determined using reverse transcriptase-polymerase chain reaction and in situ hybridization. The sequence of the rat VACM-1 cDNA was determined and found very homologous to the rabbit and human sequences. Both VACM-1 and AII/AVP receptor genes were widely expressed in the brain, but differed according to the cell type studied. Glial cells were very faintly labelled. The epithelial cells of the choroid plexuses, the ependymal cells and the pia mater were all labelled. Both genes were most active in neurones throughout the CNS. VACM-1 and AII/AVP receptors were detected in neurones previously shown to possess V1a and V1b vasopressin receptors, and/or the AT1 and AT2 angiotensin II receptors in many brain areas. This was the case for the magnocellular neurones of the supraoptic and paraventricular nuclei of the hypothalamus. We suggest that the VACM-1 and AII/AVP receptors may account for the V2-like responses to vasopressin by these neurones which lack a genuine V2 vasopressin receptor2. sitaatti.
VACM-1, a cullin gene family member, regulates cellular signaling
Vasopressin-activated Ca(2+)-mobilizing (VACM-1) receptor binds arginine vasopressin (AVP) but does not have amino acid sequence homology with the traditional AVP receptors. VACM-1, however, is homologous with a newly discovered cullin family (CUL5) of proteins that has been implicated in the regulation of cell cycle through the ubiquitin-mediated degradation of cyclin-dependent kinase inhibitors. Because cell cycle processes can be regulated by the transmembrane signal transduction systems, the effects of VACM-1 expression on the Ca(2+) and cAMP-dependent signaling pathway were examined in a stable cell line expressing VACM-1 in VACM-1 transfected COS-1 cells and in cells cotransfected with VACM-1 and the adenylyl cyclase-linked V(2) AVP receptor cDNAs. Expression of the VACM-1 gene reduced basal as well as forskolin- and AVP-stimulated cAMP production. In cells cotransfected with VACM-1 and the V(2) receptor, the AVP- and forskolin-induced increases in adenylyl cyclase activity and cAMP production were inhibited. The inhibitory effect of VACM-1 on cAMP production could be reversed by pretreating cells with staurosporin, a protein kinase A (PKA) inhibitor, or by mutating S730A, the PKA-dependent phosphorylation site in the VACM-1 sequence. The protein kinase C specific inhibitor Gö-6983 further enhanced the inhibitory effect of VACM-1 on AVP-stimulated cAMP production. Finally, AVP stimulated D-myo-inositol 1,4, 5-trisphosphate production both in the transiently transfected COS-1 cells and in the stable cell line expressing VACM-1, but not in the control COS-1 and Chinese hamster ovary cells. Our data demonstrate that VACM-1, the first mammalian cullin protein to be characterized, is involved in the regulation of signaling.
3.
PACAP ( ylin hormonaalinen säätö osoittaa yhteistyötä hypofyysin neuronaalisten vasopressiinineuronien reseptorin ja myös RAAS-järtestelmän kanssa kaksoireseptorin uodostavan Arg-vasopressiinireseptorin kanssa
Pituitary adenylate cyclase-activating polypeptide (PACAP): a novel regulator of vasopressin-containing neurons
Pituitary adenylate cyclase-activating polypeptide (PACAP) was localized in nerve terminals that innervate arginine-vasopressin (AVP)-containing neurons in the rat hypothalamic supraoptic nucleus (SON).
PACAP receptor (PACAPR) mRNA was expressed at high-levels in AVP-containing neurons in the SON, but at very low-levels in oxytocin-containing neurons. PACAPR-like immunoreactivity was found in SON and it was observed in the post-synaptic membranes as well as on the rough endoplasmic reticulum (rER) and cytoplasmic matrices in the magnocellular neurons.
Doses of PACAP in the nanomolar range increased cytoplasmic Ca2+ concentrations ([Ca2+]i) in AVP-containing neurons; the increase in [Ca2+]i was inhibited by a protein kinase A blocker. These findings suggest that PACAP serves as a transmitter and/or modulator and the activation of PACAPR stimulates a cAMP-protein kinase A pathway which in turn evokes the Ca2+ signaling system. It is hypothesized that PACAP regulates the functions of AVP-containing neurons which participate in the control of plasma osmolarity and blood pressure.
(Kommenttini: Sars-2 painottaa kovasti iositoliaineenvaihdunnan tuotteita ja kalsiumin vikasäätöä).
4. Arginiii-vasopressiinigeein prosesoitumisesta peptidiksi.
Vertailuoksytosiii ja desmopresisiimolekyyliin.
AVP reseptorit.
Myös Akvaporiinista AQP2
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