The CGRP receptor can couple via pertussis toxin sensitive and insensitive G proteins.
Swiss 3T3 cell lines were constructed co-expressing receptor activity modifying protein (RAMP) 1 with the calcitonin receptor-like receptor (CRLR), and showed 125I-calcitonin-gene-related peptide (CGRP) 1 binding indicative of a type I CGRP receptor. Application of CGRP1 led to an increase in cAMP, which in 2/5 cell lines was augmented following pertussis toxin (PTX) pre-treatment. In Xenopus oocytes, expression of RAMP1, which potentiates an endogenous CGRP receptor, led to constitutive activation of co-expressed GIRK potassium channels. This potassium current was increased following CGRP application or co-expression of CRLR, but decreased by PTX or co-expression of transducin. We conclude that the CGRP receptor can signal to both PTX sensitive and insensitive G proteins.
Main
M J
MJ
Receptor Systems, Glaxo Wellcome Research Ltd., Medicines Research Centre, Stevenage, Hertfordshire, UK.
Brown
J
J
Brown
S
S
Fraser
N J
NJ
Foord
S M
SM
D016475:3T3 Cells; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology; D058286:Calcitonin Receptor-Like Protein; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009865:Oocytes / Q000502:physiology; D037342:Pertussis Toxin; D015221:Potassium Channels / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D058262:Receptor Activity-Modifying Protein 1; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin / Q000235:genetics / Q000502:physiology*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D015293:Transducin / Q000235:genetics / Q000502:physiology; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014981:Xenopus
C545578:CALCRL protein, human; D058286:Calcitonin Receptor-Like Protein; C545579:Calcrl protein, mouse; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C545502:RAMP1 protein, human; C545505:Ramp1 protein, mouse; D058262:Receptor Activity-Modifying Protein 1; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin; D018015:Receptors, Calcitonin Gene-Related Peptide; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D015293:Transducin; D015740:Calcitonin Gene-Related Peptide