title: Intracellular calcium increase and somatodendritic vasopressin release by vasopressin receptor agonists in the rat supraoptic nucleus: involvement of multiple intracellular transduction signals.
abstract: Vasopressin neurones of the supraoptic nucleus are autoregulated by vasopressin released from their soma and dendrites. Vasopressin binds to specific autoreceptors to trigger an influx of Ca(2+), and this response involves both phospholipase C (PLC) and adenylate cyclase (AC) pathways that, in the periphery, are activated by V(1) (V(1a) and V(1b))- and V(2)-type receptors. To investigate the pathways involved in the [Ca(2+)](i) response, [Ca(2+)](i) measurements were made on freshly dissociated neurones using Fura-2 microspectrofluorimetry, and vasopressin release was measured from isolated supraoptic nuclei. The [Ca(2+)](i) increase and vasopressin release induced by the V(1a) agonist were strongly inhibited by a PLC blocker, an IP(3) receptor antagonist, and a PKC blocker. An AC inhibitor did not affect the V(1a) response, while PKA inhibitors significantly reduced the V(1a)-induced [Ca(2+)](i) and release responses. The [Ca(2+)](i) increase and vasopressin release elicited by the V(2) agonist were attenuated not only by AC pathway blockers, but also by PLC inhibitors. Surprisingly, the V(1b) agonist showed no [Ca(2+)](i) or vasopressin release response. In conclusion, the V(1a) agonist activates both PLC and AC pathway, confirming the functional expression of a V(1a) vasopressin receptor on vasopressin neurones. The V(2) agonist activation of both PLC and AC pathways could result from an action on the PLC-linked unknown receptor, and/or the AC-linked dual angiotensin II-vasopressin receptor.
authors.affiliation: Department of Biomedical Sciences, University of Edinburgh Medical School, Edinburgh, UK. n.sabatier@ed.ac.uk
authors.forename: N
authors.initials: N
authors.lastname: Sabatier
authors.forename: I
authors.initials: I
authors.lastname: Shibuya
authors.forename: G
authors.initials: G
authors.lastname: Dayanithi
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D017660:Autoreceptors / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D000072181:Inositol Polyphosphate 5-Phosphatases; D007424:Intracellular Fluid / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000819:agonists* / Q000145:classification / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013495:Supraoptic Nucleus / Q000166:cytology / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism / Q000502:physiology*
chemical_list: D017660:Autoreceptors; D017483:Receptors, Vasopressin; D014667:Vasopressins; D011493:Protein Kinase C; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases