Vasopressie-induced sensitization: involvement of neurohypophyseal peptide receptors

Paule Poulin, Patricia Szot, Daniel M. Dorsa, Quentin J. Pittman

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Rats pretreated with an intracerebroventricular (i.c.v.) injection of 10 pmol of vasopressin or vasoprcssin analogs, including deamino-d-vasopressin, [pGlu1,Cyt6]vasopressin, [pGlu-Asn-Cys(Cys)]Pro-Leu-Gly-NH2, des-Gly-NH92-vasopressin, Pro-Leu-Gly-NH2, Pro-Arg-Gly-NH2, became markedly hyper-responsive to the motor effects, 24 h later, to a subsequent challenge dose of vasopressin, but not vasopressin-related peptides. A vasopressin V1 receptor antagonist, [d(CH2)15, Tyr(Me)2]vasopressin. but not the vasopressin V2 receptor antagonist, [d(CH2)15, Tyr(Et)2,Val4]vasopressin, or a more selective vasopressin V2 receptor antagonist, [d(CH2)15,d-Ile2,Ile4]vasopressin, or the oxytocin receptor antagonist, [d(CH2)15, Tyr(Me)2, Thr4,Orn8, Tyr-NH92]vasotocin ([d(CH2)15,Tyr(Me)2,Thr4,Tyr-NH92]OVT), blocked vasopressin and vasopressin analog-induced sensitization. Furthermore, both vasopressin V2 receptor antagonists were found to sensitize the brain to a subsequent vasopressin injection. This vasopressin V2 receptor antagonist-induced sensitization was also blocked by the vasopressin V1 receptor antagonist. Next. we wanted to determine if this sensitization process could involve the release of endogenous vasopressin in the brain as reflected in an amplification of vasopressin mRNA expression. However pretreatment of rats with an i.c.v. vasopressin injection was not associated with an increase in vasopressin mRNA expression in the bed nucleus of the stria terminalis, medial amygdala or the paraventricular nucleus of the hypothalamus when measured 0, 1, 3, 7, 12, or 24 h after the first vasopressin injection. As many vasopressin analogs can induce sensitization, we suggest that a novel type of receptor may be involved in the sensitization process.

Original languageEnglish (US)
Pages (from-to)29-39
Number of pages11
JournalEuropean Journal of Pharmacology
Volume294
Issue number1
DOIs
StatePublished - Dec 27 1995

Keywords

  • Neuromodulation
  • Oxytocin
  • Structure-activity

ASJC Scopus subject areas

  • Pharmacology

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