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Biphasic effects of the β‐adrenoceptor agonist, BRL 37344, on glucose utilization in rat isolated skeletal muscle
Author(s) -
Liu YongLing,
Cawthorne Michael A.,
Stock Michael J.
Publication year - 1996
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.1476-5381.1996.tb16736.x
Subject(s) - endocrinology , medicine , soleus muscle , atenolol , chemistry , stimulation , agonist , antagonist , glycogen synthase , glycogen , skeletal muscle , receptor , biology , blood pressure
1 The effects of the selective β 3 ‐adrenoceptor agonist, BRL 37344 (BRL) on glucose uptake and phosphorylation (i.e. glucose utilization; GU) and glycogen synthesis in rat isolated soleus and extensor digitorium longus (EDL) muscle preparations in vitro were investigated by use of 2‐deoxy‐[ 3 H]‐ glucose (GU) and [U‐ 14 C]‐glucose (glycogen synthesis). 2 Low concentrations of BRL (10 −11 ‐10 −9 M) significantly increased GU, with maximal increases of 30% in soleus and 24% in EDL at 10 −11 M. Neither the selective β 1 ‐adrenoceptor antagonist, atenolol (10 −8 ‐10 −6 M), nor the selective β 2 ‐adrenoceptor antagonist, ICI 118551 (10 −8 − 10 −6 M) had any effect on the stimulation of GU induced by 10 −11 M BRL. 3 High concentrations of BRL (10 −6 − 10 −5 M) caused significant inhibition (up to 30%) of GU in both soleus and EDL muscles. The inhibition at 10 −6 M BRL was blocked completely by 10 −6 and 10 −7 M ICI 118551 in soleus, and by 10 −6 ‐10 −8 M ICI 118551 in EDL; atenolol (10 −8 − 10 6 M) had no effect. 4 Another selective β 3 ‐adrenoceptor agonist, CL 316,243, also caused a significant stimulation of muscle GU, with maximal increases of 43% at 10 −9 M in soleus and 45% at 10 −10 M in EDL. The stimulation of GU declined with further increases in the concentration of CL 316,243, but no inhibition of GU was seen, even at the highest concentration (10 −5 M) tested. 5 BRL at 10 −5 M inhibited completely insulin‐stimulated glycogen synthesis in both soleus and EDL, but this inhibitory effect of BRL was abolished by 10 −6 M ICI 118551. BRL at 10 −11 M (with or without 10 −6 M ICI 118551) had no effect on insulin‐stimulated glycogen synthesis. 6 It is concluded that: (i) low (nM) concentrations of BRL; (iii) inhibition of GU via β 2 ‐adrenoceptor activation is associated with inhibition of glycogen synthesis, possibly due to activation of glycogenolysis; (iv) the opposing effects of β 2 ‐adrenoceptor and atypical β‐adrenoceptor activation on GU suggest that in skeletal muscle these adrenoceptors are linked to different post‐receptor pathways.