ISSN:
0021-9541
Keywords:
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Medicine
Notes:
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.
Additional Material:
4 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcp.1041490217
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