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In this paper, (-)-[3H]dihydroalprenolol ([3H]DHA) binding, cyclic AMP (cAMP) and free fatty acid (FFA) accumulations of fat cells from both the genetically obese Zucker fatty rats and Wistar rats were studied for the purpose of recognizing the characteristics of lipolytic activities in the obese animals. In the experiments of [3H]DHA binding on intact fat cells, it was revealed that some of [3H]DHA bindings had properties of a beta-adrenergic receptor, while the others had those of a non-beta-receptor, the latter showing the lack of stereospecificity and the failure to compete in a potent manner against beta-adrenergic agonist. This concentration of phentolamine displayed no apparent effect on the ability of isoproterenol to stimulate cAMP accumulation in the fat cells. However, even in the presence of 10(-4)M phentolamine, non-beta-receptor binding was observed by increasing the concentration of [3H]DHA to higher than 10(-9)M. Accordingly, the experimental conditions of [3H]DHA binding were as follows: 3 approximately 15 x 10(4) fat cells preincubated with 10(-4)M phentolamine for 5 min were incubated for 12 min in modified Krebs-Ringer phosphate buffer (KRP, pH 7.4, 37 degrees C), at a final volume of 1 ml containing 0.3% bovine serum albumin, 3 x 10(-10)M [3H]DHA and competitors. The content of the tube were then rapidly filtered under vacuum through a single Whatman GF/C filter (pore size 1.2 micrometers). Computer-analysis of the resulting inhibition curve provided total binding, slope factor, half-maximally inhibitory concentration and non-specific binding. In this condition, [3H]DHA binding on intact fat cells showed the stereospecificity and the equilibrium dissociation constant of (-)- and (+)-propranolol, (-)-alprenolol and (-)-isoproterenol approximate to those expected from the biological activities, displaying properties consistent with those of a beta-adrenergic receptor. cAMP and FFA were determined in cell plus medium after incubation for 5 and 30 min, respectively. The data obtained from the [3H]DHA binding studies and cAMP measurements indicate that the equilibrium dissociation constant, maximal binding and isoproterenol-stimulated cAMP accumulations per 10(6) cells did not differ significantly between the Zucker fatty rats and Wistar rats.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of acute and chronic stress on escape behavior, brain norepinephrine (NE) concentration and beta-receptor binding was examined, and the mechanism of adaptation to chronic stress was discussed in terms of both behavioral and neurochemical standpoint. The rats were divided into an acute stress group (AS), chronic stress group (CS) and control group (C). The rats of AS experienced a single stress session. The rats of CS received 5 separate sessions. The rats of each group were examined by escape test, or killed for the purpose of measurement of beta-receptor binding and NE concentration 30 min after the final shock. The latency of escape test of AS was significantly greater than that of C. On the other hand, the latency of CS, and cortex beta-receptor binding of CS was significantly lower than that of C. However, beta-receptor binding of hypothalamus of AS and CS was not different from that of C. These results indicate that adaptation to chronic stress occurs with respect to escape behavior, and its neurochemical background relates with the acceleration of NE turnover and down regulation of beta-receptor sensitivity of cerebral cortex.

In conscious rabbits, the intravenous administration of pindolol (1.25 mg/kg), propranolol (1 mg/kg) and alprenolol (2 mg/kg) induced a highly significant decrease of mean arterial blood pressure and significant bradycardia. In the same model, the intravenous administration of saline, indomethacin, and clidanac did not affect the mean arterial blood pressure and heart rate. Pretreatment with indomethacin and clidanac reduced the effect of these beta-blockers on the mean arterial blood pressure and had no effect on the heart rate. Treating of the guinea pig heart homogenate with 1 microM indomethacin or clidanac decreased the number of beta-adrenoceptors without changing their affinity. These results suggest that indomethacin and clidanac interfere with beta-adrenoceptor-mediated effects.

The effect of the thyroid hormone(T4) on the internalization of beta-adrenergic receptors in isolated hepatocytes was examined. Uptake of [3H]-dihydroalprenolol(DHA) by the cells, which were prepared from untreated-rats, was increased by the time-dependent manner in vitro. The amount of incorporated-[3H]-DHA was decreased by further incubation in the presence of 10(-5) M of d, 1-isoproterenol. However, about 30% of incorporated-[3H]-DHA remained in the cells by this treatment. The amount of this [3H]-DHA remaining in the cells was lowered by pretreatment of the cells with methylamine, monodansylcadaverine, d, 1-isoproterenol or d, 1-propranolol. Then the amount of this [3H]-DHA was recognized as an internalized-receptor-hormone(or -DHA) complex. The total uptake(internalized- + membrane bound-) of [3H]-DHA by the cells was not significantly different between the thyroidectomized (TX + Saline) and T4-treated-thyroidectomized(TX + T4) rats. However, the rate of disappearance of incorporated-[3H]-DHA was greater in the TX + T4 animals compared to that in the TX + Saline animals. In the cells obtained from the TX + T4 animals, internalized-[3H]-DHA was significantly higher than that of the TX + Saline animals. The number of membrane associated beta adrenergic receptors was significantly lower in the TX + T4 group. These results suggest that the thyroid hormone induces an acceleration of internalization of beta adrenergic receptors in hepatocytes.