Muscarinic receptor pathways in nonfailing and failing human heart

Hershberger, Ray E.; Kimball, J.A.; Minobe, Wayne; Rasmussen, Randy; Bristow, Michael R.

doi:10.1016/0735-1097(90)92402-n

Cited by 2 publications

(1 citation statement)

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“…In contrast, multiple receptors 27 -29 or receptor pathways 12 -30 in failing human ventricular myocardium are apparently not altered, including the H 2 histamine receptor pathway, 12 -27 the apreceptor, 28 the A! adenosine receptor pathway, 30 and the calcium channel-dihydropyridine receptor. The lack of alteration of these multiple receptors in failing human heart suggests that generalized or nonspecific panreceptor processes probably do not occur.…”

Section: Discussionmentioning

confidence: 99%

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

Anderson

Bristow

1989

Circulation Research

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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.

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Section: Discussionmentioning

confidence: 99%