Inhibition of vasopressin action in vascular smooth muscle by the V1 antagonist OPC-21268

Xiaomei Li, Andreas Kribben, Eric Wieder, Phoebe Tsai, Raphael A. Nemenoff, Robert W. Schrier

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

In vascular smooth muscle cells arginine vasopressin acting through the V1 receptor increases intracellular Ca2+, leading to vasoconstriction. Recent studies have also shown that vasopressin activates mitogen-activated protein kinase (MAP kinase), which may contribute to vasopressin-induced hypertrophy of vascular smooth muscle cells. We examined the ability of an orally active, nonpeptide selective V1 antagonist (OPC-21268) to block vasopressin binding and postreceptor signaling in these cells. [3H]Vasopressin binding at 2 x 10-9 mol/L was half-maximally blocked at 10-9 mol/L OPC-21268. To compare effects of OPC-21268 on binding and postreceptor signaling, we stimulated cells with 10-8 mol/L vasopressin. At this vasopressin concentration, half-maximal inhibition of binding occurred at 5 x 10-9 mol/L OPC-21268. Half-maximal inhibition of Ca2+ efflux or increases in intracellular free Ca2+ required higher concentrations of antagonist (10-7 mol/L), and half-maximal inhibition of vasopressin- stimulated MAP kinase was observed only at 10-6 mol/L OPC-21268. These results indicate that this agent selectively blocks both vasopressin binding and postreceptor signaling in vascular smooth muscle cells. The requirement of higher concentrations of OPC-21268 for blocking increases in intracellular Ca2+ and activation of MAP kinase suggests that binding to a fraction of V1 receptors generates maximal levels of second messengers or the existence of subtypes of the V1 receptor with differential affinity for this antagonist. These data have implications for the clinical use of this compound.

Original languageEnglish (US)
Pages (from-to)217-222
Number of pages6
JournalHypertension
Volume23
Issue number2
StatePublished - Feb 1994
Externally publishedYes

Fingerprint

OPC 21268
Vasopressins
Vascular Smooth Muscle
Vasopressin Receptors
Mitogen-Activated Protein Kinases
Smooth Muscle Myocytes
Arginine Vasopressin
Second Messenger Systems
Vasoconstriction

Keywords

  • argipressin
  • calcium
  • muscle, smooth, vascular
  • protein kinases

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Li, X., Kribben, A., Wieder, E., Tsai, P., Nemenoff, R. A., & Schrier, R. W. (1994). Inhibition of vasopressin action in vascular smooth muscle by the V1 antagonist OPC-21268. Hypertension, 23(2), 217-222.

Inhibition of vasopressin action in vascular smooth muscle by the V1 antagonist OPC-21268. / Li, Xiaomei; Kribben, Andreas; Wieder, Eric; Tsai, Phoebe; Nemenoff, Raphael A.; Schrier, Robert W.

In: Hypertension, Vol. 23, No. 2, 02.1994, p. 217-222.

Research output: Contribution to journalArticle

Li, X, Kribben, A, Wieder, E, Tsai, P, Nemenoff, RA & Schrier, RW 1994, 'Inhibition of vasopressin action in vascular smooth muscle by the V1 antagonist OPC-21268', Hypertension, vol. 23, no. 2, pp. 217-222.
Li X, Kribben A, Wieder E, Tsai P, Nemenoff RA, Schrier RW. Inhibition of vasopressin action in vascular smooth muscle by the V1 antagonist OPC-21268. Hypertension. 1994 Feb;23(2):217-222.
Li, Xiaomei ; Kribben, Andreas ; Wieder, Eric ; Tsai, Phoebe ; Nemenoff, Raphael A. ; Schrier, Robert W. / Inhibition of vasopressin action in vascular smooth muscle by the V1 antagonist OPC-21268. In: Hypertension. 1994 ; Vol. 23, No. 2. pp. 217-222.
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