Vasopressin mediates neuroprotection in mice by stimulation of V1 vasopressin receptors: influence of PI-3 kinase and gap junction inhibitors.
Neuroprotective effect of vasopressin analogues, arginine Vasopressin (AVP) and lysine Vasopressin (LVP) was evaluated against MgCl2 induced cerebral ischemia model. AVP significantly prevented (P < 0.01) MgCl2 (1M) induced cerebral ischemia as compared to lysine Vasopressin (LVP) which was less effective (P < 0.05). Pretreatment with PI-3 kinase inhibitors, Wortmannin and LY-294002 (50 microg/kg, ip) significantly attenuated the protective effects of vasopressin. AVP was also effective in reducing the maximal electroshock (MES) induced convulsive time and this protective effect was blocked by PI-3 kinase inhibitors. On the other hand, pretreatment with gap junction intracellular communication (GJIC) blocker, mephenamic acid (30 mg/kg, ip) significantly potentiated the MgCl2 induced cerebral ischemia. This enhancement of cerebral ischemia was not reversed by vasopressin analogue, LVP. The role of V1 vasopressin receptor was evaluated by pretreating the animals with non-selective V1 receptor antagonist, des Gly-NH2, d (CH2)5 [D-Tyr2, Thr4] OVT which reversed the effects of AVP suggesting a role for vasopressin V1 receptors. This study suggests that neurohypophyseal hormone, AVP is neuroprotective against MgCl2 induced cerebral ischemia and this effect is modulated by PI-3 kinase enzyme inhibitors and protein kinase C inhibitors through possible influence on the cerebral vascular tone. This study suggests that gap junctions have potential role in the induction of MgCl2 induced cerebral ischemia.
Tyagi
Manoj G
MG
Department of Pharmacology, Christian Medical College, Vellore 632 002, India. tyagi 243 @ yahoo.co.in
Parthiban
K V
KV
D000818:Animals; D017629:Gap Junctions / Q000187:drug effects*; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017483:Receptors, Vasopressin / Q000819:agonists*; D014667:Vasopressins / Q000494:pharmacology*
D018696:Neuroprotective Agents; D017483:Receptors, Vasopressin; D014667:Vasopressins; D019869:Phosphatidylinositol 3-Kinases