Pharmacological characterization of a receptor for calcitonin gene-related peptide on rat, L6 myocytes

Br J Pharmacol. 1992 Feb;105(2):441-7. doi: 10.1111/j.1476-5381.1992.tb14272.x.


1 The L6 myocyte cell line expresses high affinity receptors for calcitonin gene-related peptide (CGRP) which are coupled to activation of adenylyl cyclase. The biochemical pharmacology of these receptors has been examined by radioligand binding or adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation. 2 In intact cells at 37 degrees C, human and rat alpha- and beta-CGRP all activated adenylyl cyclase with EC50s of about 1.5 nM. A number of CGRP analogues containing up to five amino acid substitutions showed similar potencies. In membrane binding studies at 22 degrees C in 1 mM Mg2+, the above all bound to a single site with IC50s of 0.1-0.4 nM. 3 The fragment CGRP(8-37) acted as a competitive antagonist of CGRP stimulation of adenylyl cyclase with a calculated Kd of 5 nM. The Kd determined in membrane binding assays was lower (0.5 nM). 4 The N-terminal extended human alpha-CGRP analogue Tyro-CGRP activated adenylyl cyclase and inhibited [125I]-iodohistidyl-CGRP binding less potently than human alpha-CGRP (EC50 for cyclase = 12 nM, IC50 for binding = 4 nM). 5 The pharmacological profile of the L6 CGRP receptor suggests that it most closely resembles sites on skeletal muscle, cardiac myocytes and hepatocytes. The L6 cell line should be a stable homogeneous model system in which to study CGRP mechanisms and pharmacology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / metabolism
  • Cell Line
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • Inosine Triphosphate / metabolism
  • Iodine Radioisotopes
  • Kinetics
  • Muscles / cytology
  • Muscles / metabolism*
  • Radioligand Assay
  • Rats
  • Receptors, Calcitonin
  • Receptors, Cell Surface / drug effects*


  • Iodine Radioisotopes
  • Receptors, Calcitonin
  • Receptors, Cell Surface
  • Inosine Triphosphate
  • Cyclic AMP
  • Calcitonin Gene-Related Peptide