PMID- 9219858
OWN - NLM
STAT- MEDLINE
DCOM- 19970910
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 759
IP  - 1
DP  - 1997 Jun 6
TI  - Proconvulsive effect of vasopressin; mediation by a putative V2 receptor subtype 
      in the central nervous system.
PG  - 18-23
AB  - Subcutaneously (s.c.) administered [Arg8]vasopressin (AVP) potentiated seizures 
      induced by intracerebroventricular (i.c.v.) injection of 1.95 mg pilocarpine (a 
      muscarinic cholinergic agonist). A bell-shaped relation between dose and effect 
      was found. I.c.v. pretreatment with a V1, V2 or oxytocin receptor antagonist was 
      performed to determine whether and what type of receptor is involved in this 
      proconvulsive effect of vasopressin. For these experiments a higher dose of 
      pilocarpine (2.4 mg i.c.v.) was injected. This caused seizures in a slightly but 
      not significantly higher percentage of the rats. A dose-dependent protective 
      action of the V2 receptor antagonist d(CH2),[D-Ile2,Ile4]AVP (effective doses 
      were 25 and 125 ng) on seizures was found. A reduction was observed in the number 
      of animals that developed tonic-clonic convulsions. Neither the V1 receptor 
      antagonist d(CH2)5[Tyr(Me)2]AVP nor the oxytocin receptor antagonist 
      desGly(NH2)9d(CH2)5[Tyr(Me)2Thr4]OVT possessed anti-convulsive activity. 
      Subsequently the type of receptor was studied in detail with fragments of AVP 
      with either V1 or V2 activity. AVP (with V1 and V2 affinity) (1 and 3 microg 
      s.c.) potentiated pilocarpine (1.95 mg) induced seizures. Vasotocin and oxytocin 
      were without effect. Interestingly neither s.c. nor i.c.v. administration of the 
      selective kidney type vasopressin receptor (V2) agonist dDAVP potentiated 
      pilocarpine induced seizures. Several selective antidiuretic agonists (V2), such 
      as d[Val4]AVP, d[Phe2,Val4,D-Arg8]vasopressin (3 microg), 
      [Val4,D-Arg8]vasopressin (3 microg) and d[Val4,D-Arg8]vasopressin (3 microg) were 
      active. Other selective antidiuretic compounds, such as [Val4]AVP, dAVP, 
      d[Tyr(Me)2]AVP and HO[D-Arg8]vasopressin (3 microg) did not influence seizures. 
      These results demonstrate that a combination of substitution of aminoacid 4 (Gln) 
      by Val and to a lesser extent deamination and the D-arginine form yield an active 
      molecule, which can potentiate pilocarpine induced seizures and suggest the 
      existence of a V2 receptor subtype in the brain.
FAU - Croiset, G
AU  - Croiset G
AD  - Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, 
      Utrecht University, Netherlands. g.croiset@med.ruu.nl
FAU - De Wied, D
AU  - De Wied D
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Antidiuretic Hormone Receptor Antagonists)
RN  - 0 (Muscarinic Agonists)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Oxytocin)
RN  - 0 (Receptors, Vasopressin)
RN  - 01MI4Q9DI3 (Pilocarpine)
RN  - 113-79-1 (Arginine Vasopressin)
RN  - 50-56-6 (Oxytocin)
RN  - 87619-87-2 (argipressin (4-9))
RN  - ENR1LLB0FP (Deamino Arginine Vasopressin)
RN  - W6S6URY8OF (Vasotocin)
SB  - IM
MH  - Animals
MH  - Antidiuretic Hormone Receptor Antagonists
MH  - *Arginine Vasopressin/pharmacology
MH  - Brain/*metabolism
MH  - Deamino Arginine Vasopressin/pharmacology
MH  - Drug Synergism
MH  - Injections, Intraventricular
MH  - Male
MH  - Muscarinic Agonists
MH  - Oxytocin/pharmacology
MH  - Peptide Fragments/pharmacology
MH  - Pilocarpine
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Oxytocin/antagonists & inhibitors
MH  - Receptors, Vasopressin/agonists/*physiology
MH  - Seizures/*chemically induced
MH  - Vasotocin/pharmacology
EDAT- 1997/06/06 00:00
MHDA- 1997/06/06 00:01
CRDT- 1997/06/06 00:00
PHST- 1997/06/06 00:00 [pubmed]
PHST- 1997/06/06 00:01 [medline]
PHST- 1997/06/06 00:00 [entrez]
AID - S0006-8993(97)00070-X [pii]
AID - 10.1016/s0006-8993(97)00070-x [doi]
PST - ppublish
SO  - Brain Res. 1997 Jun 6;759(1):18-23. doi: 10.1016/s0006-8993(97)00070-x.