Characterization of the calcitonin gene-related peptide receptor in mouse T lymphocytes.
We have identified and characterized specific binding for calcitonin gene-related peptide (CGRP) in mouse T lymphocytes. The binding of 125I-CGRP to mouse lymphocytes was reversible and the rate of dissociation of 125I-CGRP increased with the addition of the guanine triphosphate nucleotide analog, Gpp(NH)p. Saturation experiments, and Scatchard analysis indicated two classes of binding sites for CGRP; the apparent dissociation constants (KD) were 3.5 X 10(-10)M for high affinity binding sites (Bmax, 265 sites/cell) and 4.8 X 10(-8)M for low affinity binding sites (Bmax, 13,000 sites/cell). The KD value for the high affinity binding sites is roughly comparable to the IC50 and ED50 values for inhibition of T lymphocyte proliferation and increase in the cyclic AMP concentration in these cells, respectively. 125I-CGRP bound to mouse T lymphocytes was displaced by unlabeled CGRP with an IC50 value of 3.2 X 10(-10)M; salmon or human calcitonins did not inhibit the specific binding up to 1 X 10(-6)m. Our studies suggest that CGRP may be an important immunoregulatory molecule, and implicate it in the regulation of T cell function.
Umeda
Y
Y
Department of Chemotherapy and Biochemistry, Nippon Roche Research Center, Kamakura, Japan.
Arisawa
M
M
D000818:Animals; D001665:Binding Sites; D002116:Calcitonin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000378:metabolism; D013601:T-Lymphocytes / Q000032:analysis* / Q000378:metabolism
D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D002116:Calcitonin; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide