Differential calcitonin gene-related peptide (CGRP) and amylin binding sites in nucleus accumbens and lung: potential models for studying CGRP/amylin receptor subtypes.
Calcitonin gene-related peptide (CGRP), a 37-amino-acid peptide, is a member of a small family of peptides including amylin or islet amyloid polypeptide and salmon calcitonin. These related peptides have been shown to display similar effects on in vitro and in vivo carbohydrate metabolism. The present study was initiated to identify and characterize the binding sites for these peptides in lung and nucleus accumbens membranes prepared from pig and guinea pig. Both tissues in either species displayed high-affinity (2-[125I]iodohistidyl10)humanCGRP alpha ([125I]hCGRP alpha) binding (IC50 = 0.4-7.7 nM), which was displaced by hCGRP8-37 alpha with equally high affinity (IC50 = 0.4-7.3 nM). High-affinity binding for [125I]Bolton-Hunter human amylin ([125I]BH-h-amylin) was also observed in these tissues (IC50 = 0.2-6.0 nM). In membranes from the nucleus accumbens of both species, salmon calcitonin competed for amylin binding sites with high affinity (IC50 = 0.1 nM) but was poor in competing for amylin binding in lung membranes. Rat amylin8-37 competed for [125I]hCGRP alpha binding with higher affinity (IC50 = 5.4 nM) compared with [125I]BH-h-amylin binding (IC50 = 200 nM) in porcine nucleus accumbens, whereas in guinea pig nucleus accumbens, the IC50 values for rat amylin8-37 were 117 and 12 nM against [125I]hCGRP alpha and [125I]BH-h-amylin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Aiyar
N
N
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
Baker
E
E
Martin
J
J
Patel
A
A
Stadel
J M
JM
Willette
R N
RN
Barone
F C
FC
D000262:Adenylyl Cyclases / Q000378:metabolism; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002116:Calcitonin / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006168:Guinea Pigs; D007457:Iodine Radioisotopes; D058228:Islet Amyloid Polypeptide; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000378:metabolism*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism*; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide / Q000378:metabolism*; D013388:Succinimides; D013552:Swine
D000682:Amyloid; D007457:Iodine Radioisotopes; D058228:Islet Amyloid Polypeptide; D018015:Receptors, Calcitonin Gene-Related Peptide; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide; D013388:Succinimides; C022581:Bolton-Hunter reagent; C028815:salmon calcitonin; D002116:Calcitonin; D000262:Adenylyl Cyclases; D015740:Calcitonin Gene-Related Peptide