Premium
Acute effects of the β 3 ‐adrenoceptor agonist, BRL 35135, on tissue glucose utilisation
Author(s) -
Liu YongLing,
Stock Michael J.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb13287.x
Subject(s) - atenolol , medicine , endocrinology , brown adipose tissue , adipose tissue , antagonist , propranolol , white adipose tissue , chemistry , insulin , in vivo , extensor digitorum muscle , soleus muscle , skeletal muscle , biology , receptor , blood pressure , microbiology and biotechnology
1 The acute effects of BRL 35135 (BRL) on tissue glucose utilisation index (GUI) in vivo were investigated in anaesthetized rats by use of 2‐deoxy‐[ 3 H]‐glucose. 2 Intravenous injection of BRL caused a dose‐dependent increase in GUI in skeletal muscle, and white and brown adipose tissue; plasma insulin and fatty acid concentrations were also increased. Chronic treatment with BRL added to the diet caused a 34 fold increase in basal GUI of brown adipose tissue (BAT), but had no effect on GUI in other tissues. After chronic treatment, the acute tissue response to an intravenous maximal dose of BRL had disappeared completely in all tissues apart from the soleus muscle. 3 A high dose (20 mg kg −1 ) of the non‐selective β‐antagonist, propranolol, inhibited the acute effect of BRL on GUI in BAT, but failed to affect GUI in muscle. A lower dose (1 mg kg −1 ) of the antagonist also inhibited the BAT response, but had little or no effect on the response in Type I (working) muscles such as soleus and adductor longus (ADL), and potentiated the response in Type II (non‐working) muscles such as tibialis and extensor digitorium longus (EDL). 4 A low dose (1 mg kg −1 ) of the selective β 1 ‐antagonist, atenolol, had no effect on the BRL response but the same dose of the selective β 2 ‐antagonist, ICI 118551, potentiated significantly the effect of BRL on GUI in most muscles without altering plasma insulin levels. 5 It is concluded that: (i) the heterogeneous tissue responses of different muscle fibre types in the presence of β‐antagonists indicates that BRL affects muscle GUI directly, in addition to effects mediated by increases in plasma insulin concentration; (ii) the resistance of the BRL response to conventional β‐adrenoceptor antagonists implicates an atypical adrenoceptor mediating the GUI response in skeletal muscle, but this may not be identical to the adipose tissue β 3 ‐adrenoceptor; (iii) the potentiation of BRL responses by ICI 118551 indicates an inhibitory β 2 ‐adrenoceptor‐mediated component in the muscle GUI response to BRL.