Autoradiographic distribution and receptor binding profile of [125I]Bolton Hunter-rat amylin binding sites in the rat brain.
Amylin is a recently isolated peptide from amyloid plaques in noninsulin-dependent diabetic patients and showed high sequence homology with calcitonin gene-related peptide. We investigated the distribution and the binding profile of [125I]Bolton Hunter-rat amylin ([125I]BH-rat amylin) binding sites in the rat brain, as well as the affinity of rat amylin for [125I]hCGRP alpha binding sites in the brain, atrium (CGRP1 receptor-enriched tissue) and vas deferens (CGRP2 receptor-enriched tissue). High amounts of high affinity [125I]BH-rat amylin binding sites were observed in the nucleus accumbens, various hypothalamic nuclei, amygdaloid body, dorsal raphe, tegmental and parabrachial nuclei and the locus ceruleus. Interestingly, both rat amylin and salmon calcitonin revealed low nanomolar affinities (2-19 nM) for [125I] BH-rat amylin binding sites in the various brain areas, whereas human calcitonin gene-related peptide-alpha (hCGRP alpha) showed lower affinities ranging between 13 to 150 nM. Moreover, the affinity of rat amylin was much lower than that of hCGRP alpha for [125I]hCGRP alpha binding in the brain, atrium and vas deferens, except for very few areas such as the nucleus accumbens and ventral striatum. Similarly, rat amylin was much weaker (100- to 400-fold) than hCGRP alpha to induce a biological effect in the atrium and vas deferens. These results thus suggest the existence of unique [125I]BH-rat amylin binding sites in the rat brain as well as limited cross-reactivity between rat amylin and [125I]hCGRP alpha receptors present in the brain, atrium and vas deferens.
van Rossum
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D
Douglas Hospital Research Centre, Verdun, Québec, Canada.
Ménard
D P
DP
Fournier
A
A
St-Pierre
S
S
Quirion
R
R
D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide / Q000378:metabolism*
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide; D015740:Calcitonin Gene-Related Peptide