Vasoactive intestinal peptide receptor in failing human ventricular myocardium exhibits increased affinity and decreased density.

We investigated vasoactive intestinal peptide (VIP)-receptor pharmacology in failing and nonfailing human ventricular myocardium by examining [125I]VIP binding in membrane fractions of left ventricle and inotropic effects of VIP in isolated right ventricular trabeculae mounted in tissue baths. [125I]VIP binding demonstrated upwardly concave, curvilinear Scatchard plots consistent with two classes of binding sites. Only the high-affinity (dissociation constant [Kd] 400-800 pM) site could be regulated by guanine nucleotides. Compared with nonfailing heart, membranes derived from failing heart exhibited a twofold reduction in the Kd of the high-affinity VIP binding site, whereas the receptor density (Bmax) was decreased by 62%. In concordance with this decreased receptor density and increased affinity, the maximal contractile response of right ventricular trabeculae from failing right ventricles was decreased by 61%, and the dose-response curve to VIP was left-shifted approximately threefold. We conclude that the VIP receptor in failing human ventricular myocardium exhibits novel regulatory behavior consisting of increased receptor affinity and decreased receptor density.

• Publication year

  1989

• Venue

  Circulation Research

• Publication date

  1989-08-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1161/01.RES.65.2.283PMID 2546693
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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