DIFFERENT PHARMACOLOGICAL CHARACTERISTICS IN L(6) AND C2C12 MUSCLE-CELLS AND INTACT RAT SKELETAL-MUSCLE FOR AMYLIN, CGRP AND CALCITONIN

1 We compared the ability of rat amylin, rat calcitonin gene-related p eptide (CGRP) and rat and salmon calcitonins to elevate cyclic AMP lev els and to inhibit [U-C-14]-glucose incorporation into glycogen in ins ulin-stimulated intact rat soleus muscle and in two cell lines derived from rodent skeletal muscle, L(6) and C2C12 2 In intact soleus muscle , both amylin (EC(50)s of 0.7-6.1 nM) and salmon calcitonin (EC(50)s O f 0.5-1.4 nM) were more potent than CGRP (EC(50)s of 5.6-15.8 nM) and were much more potent than rat calcitonin (EC(50)s of 50-137 nM) at st imulating cyclic AMP production, activating glycogen phosphorylase and inhibiting insulin-stimulated [C-14]-glycogen formation. 3 In contras t, in both L(6) and C2C12 cells, CGRP (EC(50)s Of 0.042-0.12 nM) stimu lated cyclic AMP formation and inhibited insulin-stimulated [U-C-14]-g lucose incorporation into glycogen approximately 1000 times more poten tly than amylin (EC(50)s 34-240 nM), while salmon calcitonin was witho ut measurable effect. 4 There was a correlation between elevation of c yclic AMP and inhibition of insulin-stimulated [U-C-14]-glucose incorp oration into glycogen evoked by these peptides in both intact muscle ( r(2)=0.69, P<0.0004) and muscle cell lines (r(2)=0.96, P<0.0001). 5 In conclusion, the effects of amylin, CGRP, and calcitonin on soleus mus cle glycogen metabolism appear to be mediated by adenylyl cyclase-coup led receptors which show a pharmacological profile similar to high aff inity amylin binding sites that have been previously reported in rat b rain. In contrast, the effects of amylin and CGRP in L(6) and C2C12 ro dent muscle cell lines appear to be mediated by adenylyl cyclase-coupl ed receptors that behave like CGRP receptors.