Comparative study of distribution and biochemical characterization of brain calcitonin gene-related peptide receptors...

Calcitonin gene-related peptide receptors are abundant in the brain, and the pattern of distribution of receptors is similar in the rat, pig, cow, sheep and in man. In comparison to the cerebellum (100%), only a small number of receptors were found in the ventral spinal cord (20%), cerebral white matter (20%), pituitary (27%) and hypothalamus (33%). In contrast, cerebral cortex (70%), thalamus (50%) and dorsal spinal cord (50%) contained a higher number of calcitonin gene-related peptide receptors. Overall, the highest number of receptors was observed in the pig brain followed by the rat, human, sheep and cow. IC50 values of alpha- and beta-calcitonin gene-related peptide for cerebellar membranes were 200 pM, while its antagonist calcitonin gene-related peptide(8-37) and (9-37) had an IC50 approximately 1 nM. The recently discovered 37-amino acid peptide amylin (46% homology with calcitonin gene-related peptide) displaces the membrane bound [125I]calcitonin gene-related peptide with 50-fold molar excess (IC50 = 10 nM). The only other peptide able to compete for calcitonin gene-related peptide receptor binding is salmon calcitonin, at a > 1000-fold molar excess (IC50 = 250 nM). Dissociation of [125I]calcitonin gene-related peptide from cerebellar membranes was biphasic, suggesting that calcitonin gene-related peptide receptors in the brain were heterogeneous.(ABSTRACT TRUNCATED AT 250 WORDS)