Insulin and insulin-like growth factor-I inhibit the L-type calcium channel current in rat pinealocytes.
Tyrosine phosphorylation has recently been shown to modulate ion channel activity. In the present study, the effect of growth factors on the L-type Ca2+ channel current in rat pinealocytes was investigated using the whole cell version of the patch clamp technique. Both insulin and insulin-like growth factor-I (IGF-I) inhibited the L-type Ca2+ channel current. This inhibition was dependent on concentration, with median effective concentration (EC50) values of 60 nM for insulin and 0.14 nM for IGF-I. Heat-inactivated insulin or IGF-I had no effect on the L-type Ca2+ channel current. The presence of anti-IGF-I receptor antibodies blocked the inhibitory effect of IGF-I on the L-type Ca2+ channel current. Two other growth factors, nerve growth factor and epidermal growth factor, had no effect on this current. The effects of insulin and IGF-I were blocked by lavendustin A, a tyrosine kinase inhibitor. Calphostin C, a protein kinase C inhibitor, attenuated the effect of insulin and IGF-I, whereas wortmannin, a phosphatidylinositol 3-kinase inhibitor, was ineffective. These observations indicate that insulin and IGF-I inhibit the L-type Ca2+ channel current in rat pinealocytes, and that tyrosine phosphorylation is involved in these effects of insulin and IGF-I.
Chik
C L
CL
Department of Medicine, University of Alberta, Edmonton, Canada.
Li
B
B
Karpinski
E
E
Ho
A K
AK
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology*; D004553:Electric Conductivity; D004791:Enzyme Inhibitors; D006358:Hot Temperature; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D018408:Patch-Clamp Techniques; D010636:Phenols / Q000494:pharmacology; D019000:Phosphotyrosine / Q000378:metabolism; D010870:Pineal Gland / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
D000906:Antibodies; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D007328:Insulin; D010636:Phenols; D019000:Phosphotyrosine; C062898:lavendustin A; D007334:Insulin-Like Growth Factor I; D011505:Protein-Tyrosine Kinases