AN INVESTIGATION OF THE BETA-ADRENOCEPTOR THAT MEDIATES METABOLIC RESPONSES TO THE NOVEL AGONIST BRL28410 IN RAT SOLEUS MUSCLE
AN INVESTIGATION OF THE BETA-ADRENOCEPTOR THAT MEDIATES METABOLIC RESPONSES TO THE NOVEL AGONIST BRL28410 IN RAT SOLEUS MUSCLE
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DOI：
10.1016/0006-2952(88)90186-4
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发表时间：
1988-03-01
影响因子：
5.8
通讯作者：
ARCH, JRS
中科院分区：
文献类型：
--
作者：
CHALLISS, RAJ;LEIGHTON, B;ARCH, JRS
The .beta.-adrenoceptor agonist BRL26830A selectively stimulates metabolic rate in the rat and this thermic effect is resistant to blockade by propranolol. These effets of BRL26830A are partly due to selective stimulation by its metabolite BRL28410, of brown adipocyte .beta.-adrenoceptors, these receptors being resistant to propranolol. To investigate whether the metabolic effects of BRL28410 and isoprenaline were compared for .beta.-adrenoceptor mediated responses in rat stripped soleus muscle. In addition, pA2 values for antagonism by propranolol of these responses were determined. Isoprenaline had similar EC50 values for stimulation of lactate formation (4.3 .times. 10-9 M), and inhibition of glycogen synthesis (3.4 .times. 10-9 M) and these values are similar to its reported EC50 values for stimulation of atrial rate (.beta.1-adrenoceptor-mediated) and relaxation of the uterus (.beta.2-adrenoceptor-mediated). BRL28410 had similar EC50 values for stimulation of lactate formation (3.7 .times. 10-6 M) and inhibition of glycogen synthesis (3.8 .times. 10-6 M). These values are only about two-fold less than reported values for relaxation of the uterus, but ten-fold less than reported values for stimulation of atrial rate. The pA2 value of dl-propranolol for antagonism of the effect of isoprenaline on glycogen synthesis (8.38 .+-. 0.13) was in the range expected for .beta.1- or .beta.2-adrenoceptors, but with BRL28410 as agonist the pA2 value was about one unit lower (7.39 .+-. 0.11). The .beta.-adrenoceptors that mediate the metabolic effects of BRL28410 in soleus muscle therefore differ from those that mediate atrial rat, uterine relaxation and adipocyte lipolysis. In addition, the low pA2 value of dl-propranolol versus BRL28410 in rat soleus muscle, which contrasts with the normal pA2 value previously reported for guinea-pig trachea, suggests that .beta.2-adrenoceptors in these two tissues can be differentiated with suitable pharmacological agents.
