Regulation of Heat Production of Brown Adipocytes via Typical and Atypical .BETA.-Adrenoceptors in the Rat.

Abstract

Previous studies in our laboratory demonstrated that microcalorimetry is an appropriate method for estimating the physiological function of isolated rat brown adipocytes. In the present study, to elucidate the mode of action of typical and atypical beta-adrenoceptors on heat production of this cell, the effect of novel adrenergic beta 3-agonists was compared with that of other typical adrenergic reagents by direct microcalorimetry. Isoproterenol and beta 3-agonists, BRL37344, ICI215001, and CGP12177, increased heat production in a dose-dependent manner, however, phenylephrine had no effect. Propranolol and pindolol did not increase the heat production but attenuated the effect of isoproterenol and BRL37344 in a dose-dependent manner. Molar IC50 values of propranolol and pindolol for BRL37344 were about 10(-5) and 3 x 10(-6) M, respectively, whereas those of the two antagonists for isoproterenol were about 3 x 10(-7)M. The pA2 values by Schild analysis of propranolol vs. isoproterenol and BRL37344 were 7.91 and 6.13, respectively. These results suggest that heat production may be regulated via both beta 3- and typical beta-adrenoceptors in brown adipocytes.

Heat Production by Brown Adipocytes of FOK Rats Genetically Resistant to a Hot Environment.

“…This would be advantageous to animals resistant to a hot environment. In a previous paper, we demonstrated that 10 9 M isoproterenol increased heat production in Wistar rats [17,18]. In the present study, an equivalent result was obtained in WKAH rats, but not in FOK rats, at both normal and high temperatures.…”

“…Since in heat-acclimated animals, it was found that certain suppressive modifications of the metabolic oxidative processes took place [2,4,13,21], it may be assumed that similar changes would occur in FOK rats without exposure to heat. The high concentration (10 6 M) of isoproterenol was thought to be the maximal stimulation [17,18], where the maximal heat production was similar between the two strains.…”

“…All rats were kept at 24 ± 1°C of ambient temperature, without heat exposure, until decapitation. After weighing the interscapular BAT, the brown adipocytes were isolated by the method of Bukowiecki et al [1] with some modifications [17]. Heat production by the cells was measured with and without isoproterenol either at 37.0 and 39.9°C using a microcalorimeter (Thermoactive Cell Analyzer ESCO-3000, ESCO Ltd., Tokyo) [17,18,20].…”

“…After weighing the interscapular BAT, the brown adipocytes were isolated by the method of Bukowiecki et al [1] with some modifications [17]. Heat production by the cells was measured with and without isoproterenol either at 37.0 and 39.9°C using a microcalorimeter (Thermoactive Cell Analyzer ESCO-3000, ESCO Ltd., Tokyo) [17,18,20]. After all the cells, which were suspended in a total volume of 0.5 ml, were entered increase in WKAH and FOK rats at both temperatures (ANOVA), where heat production of FOK rats was not significantly different from that of WKAH rats (unpaired ttest).…”

A Dual Component Analysis Explains the Distinctive Kinetics of cAMP Accumulation in Brown Adipocytes

“…In this respect, isoprenaline-induced responses are therefore principally different from those of selective ␤ 3 -agonists, for which we see no indication of an ␣ 1 effect. It is possible that this ␣ 1 -component may explain several recent observations on brown fat cells where the response to isoprenaline deviated from that to selective ␤ 3 -stimulation or direct adenylyl cyclase activation (41)(42)(43). That isoprenaline seems to influence the ␣ 1 -pathway to a larger extent in brown fat cells than in many other tissues may be due to the very high level of expression of ␣ 1 -receptors in brown adipose tissue, compared with the levels in other tissues (44).…”