CGRP and adrenomedullin binding correlates with transcript levels for Calcitonin Receptor-Like Receptor (CRLR) and Receptor Activity Modifying Proteins (RAMPs) in rat tissues

1 Putative receptors for CGRP and adrenomedullin have been investigated in the rat. Calcitonin Receptor-Like Receptor (CRLR), in combination with Rece ptor Activity Modifying Proteins (RAMPs) is hypothesized to bind either CGR P or adrenomedullin. The receptors known as RDC1 and L1 have also been show n to bind CGRP and adrenomedullin respectively. 2 In this study it is shown that rat CRLR cDNA specifies a CGRP receptor wh en co-transfected with RAMP-1 cDNA and an adrenomedullin receptor when co-t ransfected with either RAMP-2 or RAMP-3 cDNA in human embryonic kidney 293 cells. 3 CRLR, RAMP, RCD1 and L1 mRNA levels and CGRP and adrenomedullin receptor densities have been measured and correlated with each other in eight rat ti ssues selected for their distinctive patterns of CGRP and adrenomedullin bi nding. 4 The data are consistent with the predictions of the CRLR/RAMP model. CGRP binding correlates well with RAMP-1 mRNA levels (R = 1.0, P = 0.007), adre nomedullin binding shows a tendency to vary with RAMP-2 mRNA levels (R = 0. 85, P = 0.14) and total binding is correlated with CRLR mRNA levels (R = 0. 94, P = 0.03). The data do not support the hypothesis that RDC1 and L1 acco unt for the majority of CGRP and adrenomedullin binding respectively.