Increased β-adrenoceptor-coupled adenylate cyclase response in transplanted human hearts

Abstract

A transplanted (Tx) heart will probably compensate its sympathetic denervation by increasing the sensitivity to adrenergic stimulants. To evaluate whether this also engages the myocardial adenylate cyclase (AC) system, small endomyocardial biopsies were collected at right heart catheterization both from patients with heart Tx with no signs of rejection and from a group of patients serving as controls. In crude homogenates from these biopsies, AC activity was measured at basal conditions and following in vitro stimulation with optimal concentrations of β-receptor agonists, histamine and sodium fluoride (NaF). The Tx group exhibited a 75% (p=0.01) higher activation of AC with isoproterenol, and a 62% (p<0.05) higher AC activation with terbutaline compared with the control group. The differences in AC activation by histamine and NaF were insignificant. Thus, sympathetic denervation leads to increased activation of the β-adrenoceptor-coupled AC system, leaving the histaminergic system unaltered. The upregulation does probably engage the receptor part of the receptor—AC system exclusively, since no elevation of NaF stimulation of AC was found in the Tx hearts.

Key words:

• β-adrenoceptors
• human myocardium
• in vitro
• receptor upregulation