Characterization of functional calcitonin gene-related peptide receptors on rat lymphocytes.

摘要: Calcitonin gene-related peptide (CGRP), a vasoactive neuropeptide present in peripheral neurons, is released at local sites of inflammation. In these studies specific high affinity adenylyl cyclase linked CGRP receptors were characterized on rat lymphocytes. The distribution, affinity, and specificity was analyzed by radioligand binding. 125I-[His10]CGRP binding to lymphocytes rapid, reaching equilibrium 20 30 min 22 degrees C, dependent cell concentration. dissociation constants, Kd, for the receptor purified T B are 0.807 +/- 0.168 nM 0.387 0.072 densities 774 387 747 244 sites/cell, respectively. Competition determined that inhibits with highest (Ki = 0.192 0.073) followed human antagonist CGRP8-37. not inhibited neuropeptides substance P, calcitonin, or Y. Lymphocyte proteins identified labeling using disuccinimidyl suberate covalently cross-link its receptor. Specifically labeled visualized SDS-PAGE analysis had molecular masses 74.5 220 kDa. A third mass protein band which did penetrate gel also observed. functional studies, stimulated sustained increase cAMP an ED50 approximately 8 pM. experiments comparing optimal concentrations isoproterenol, beta 2-adrenergic agonist, CGRP, intracellular elevation after isoproterenol treatment returned basal levels min, whereas still elevated 60 treatment. response it could be completely blocked presence provides evidence modulatory role regulating lymphocyte function.