Plasma membrane-specific deficiency in cardiac beta-adrenergic receptor in streptozocin-diabetic rats

Abstract

Cell surface [3H]CGP 12177 binding sites in 10-wk streptozocin-diabetic rats decreased by 41% (P less than 0.01) compared with that in the control rats. In contrast, there was no difference in the total cell receptor concentration between the control and the diabetic rats, which was measured by hydrophobic antagonist [125I]-iodocyanopindolol binding. Forty-eight-hour in vivo insulin treatment significantly (P less than 0.05) increased cell surface beta-adrenergic receptor concentration by 37% above that in diabetic rats without any change in total receptor concentration in the cells. However in vitro treatment of 8 nM insulin, 33 mM glucose, or 10 mM 3-hydroxybutyrate for 2 h showed no effect on [3H]CGP 12177 binding. In contrast, 10 microM isoproterenol-dependent decrease and the recovery of cell surface receptors after the removal of the agonist were significantly (P less than 0.01) impaired in diabetic rats compared with those of control rats. These results indicate that only cell surface beta-adrenergic receptors decrease in diabetic rats, which may be associated with abnormalities in the receptor distribution. The decrease in cell surface receptor number closely associates with the diabetic state and is reversed by the short-term insulin treatment.

Quantitative determination of cell surface β-adrenoceptors in different rat skeletal muscles

“…β-Adrenergic receptors are internalised during agonist stimulation and some pathological situations (Kashiwagi et al 1989;Bünemann et al 1999). Trafficking of receptors must therefore be avoided during tissue preparation to obtain information of cell surface receptor density.…”

“…After the incubation, biopsies were washed briefly and incubated for 10 or 60 min in buffer with 10 mU/ml insulin (filled triangles). Control muscles (open circles) remained in control buffer and some muscles were incubated with 10 µM isoprenaline during the whole period (filled circles) (n=5 for 10 min, otherwise 8-12) stimulation, as much as 70-80% of the receptors are internalised in the heart (Kashiwagi et al 1989). The physiological significance of the difference in internalisation of β-adrenergic receptors in types-I and -II muscle fibres remains to be determined.…”

“…The responsiveness to β-adrenergic stimulation depends on the density of β-adrenoceptors in the cell membrane (Böhm et al 1997;Grady et al 1997). β-Adrenoceptors are, however, internalised during prolonged agonist stimulation and during some pathological situations (Büne-mann et al 1999;Kashiwagi et al 1989). Determination of the density of β-adrenergic receptors in the cell membrane is therefore of particular interest.…”

Changes in adenosine sensitivity in the hippocampus of rats with streptozotocin‐induced diabetes

“…These include changes of acetylcholine receptor number or affinity and sensitivity to cholinomimetics of several tissues (Latifpour et al, 1989;Carrier & Aronstam, 1987;Aronstam & Carrier, 1989). There are also marked alterations of peripheral catecholamine receptor function or sensitivity in vascular and nonvascular smooth muscle, including changes of x-adrenoceptor (Wald et al, 1988;Drukarch et al, 1989) and P-adrenoceptor mediated responses (Ingebretsen et al, 1983;Berlin et al, 1986;Ramanadhan & Tenner, 1987;Kashiwagi et al, 1989).…”

G-proteins and β-adrenergic stimulation of adenylate cyclase activity in the diabetic rat prostate

“…Previous results [16] demonstrated that STZ-induced diabetes decreases by 50% the density of ␤-adrenergic receptors in rat prostatic membranes, in accordance with the important loss of functional response observed in the present work. A diminished ␤-adrenergic receptor density has also been found in other tissues from experimental diabetic rats such as heart [29], and this was partially ascribed to a possible abnormality in receptor recycling [30]. This possibility has not been analyzed in the diabetic rat prostate.…”