Macrophages express functional receptors for calcitonin‐gene‐related peptide

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Abstract
The present study was designed to investigate whether non‐activated macrophages express calcitonin (CT) or calcitonin‐gene‐related peptide (CGRP) receptors. To this end, we first analyzed whether CT and CGRP induce a cAMP accumulation in macrophages. Macrophages were treated for 2 min with increasing concentrations of either CT or CGRP in the presence or absence of IBMX. A dose‐dependent cAMP accumulation was measured in response to CGRP with a half‐maximal effect attained with 1 nM CGRP. CT failed at all doses to induce an accumulation of cAMP. The effects of CT and CGRP on the activation of the Na‐H exchanger were next assessed by spectrofluorometry by using the pH‐sensitive dye 2,7 biscarboxyethyl‐5(6)‐carboxyfluorescein (BCECF). Steadystate pHi of macrophages in a 7.4, HCO3‐free solution (HEPES‐buffered) was 7.04 ± 0.08 (n = 22). pHi recovery following an NH4+/NH3 acid load was inhibited by the removal of Na+ or by the addition of the amiloride analog EIPA; therefore recovery is dependent on Na‐H exchange activity. CT had no effect on steady‐state pHi but CGRP increased pHi in a dose‐dependent fashion (10−12 to 10−6M). The pHi change induced by CGRP was due to the stimulation of the Na‐H exchanger as CGRP enhanced the rate of recovery (dpHi/dt) from an acid load from 45.3 to 77.2 μMs−1 (n = 8, P < 0.002) and was completely blocked by EIPA. These data indicate that CGRP both enhances the activity of the Na‐H exchanger and increases intracellular cAMP, thus demonstrating that macrophages express functional CGRP receptors.