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Combinative ligand‐receptor interactions: Effects of CAMP, epinephrine, and met‐enkephalin on RAW264 macrophage morphology, spreading, adherence, and microfilaments

Cell surface ligand‐receptor interactions play a central role in the regulation and expression of macrophage function. Included among these macrophage membrane receptors are the β‐adrenergic and opioid receptors. We studied the abilities of epinephrine, met‐enkephalin, forskolin, and adenosine 3′:5′ cyclic monophosphate (cAMP) analogues to affect macrophage morphology, spreading, and adherence. Cell spreading was quantitated by measuring the perimeters of adherent cell images recorded by videomicroscopy. Epinephrine induced a dose‐dependent decrease in macrophage spreading; at 10‐5 M epinephrine the mean perimeter was 10.4 ± 0.3μm in comparison to 15.0 ± 1.0 μm for controls. The inhibition of spreading can be blocked by the antagonist propranolol. On the other hand, met‐enkephalin induced a dose‐dependent increase in macrophage spreading, with a perimeter of 18.5 ± 1.0 μm at 10‐8 M. Since catecholamines and opioids are simultaneously released from chromaffin cells of the adrenal, we examined the combinative effects due to treatment with both ligands. When macrophages were exposed to 10‐5 M epinephrine and 10‐8 M met‐enkephalin, cell morphology and spreading were indistinguishable from that due to 10‐5 M epinephrine alone. The epinephrine dose‐response curve in the presence of 10‐8 M met‐enkephalin, was similar to that of epinephrine alone. The β‐adrenergic receptor is apparently capable of diminishing or abrogating the opioid receptor signal(s). These combinative and epinephrine‐mediated effects may be at least partially accounted for by the action of cAMP. Forskolin and the cAMP analogues N6 –2′‐O‐dibutyryladenosine 3′:5′ cyclic monophosphate (dbcAMP) and 8‐bromoadenosine 3′:5′ cyclic monophosphate (Br‐cAMP) affected cell morphology and spreading in the same fashion as epinephrine. These differences in morphology and spreading behavior were accompanied by changes in the distribution of F‐actin, as judged by phalladicin staining and fluorescence microscopy. We suggest that cAMP and microfilaments play important roles in receptor‐mediated neuroregulation of macrophage function.