Beta-adrenoceptor-mediated modulation of calcium ionophore activated polymorphonuclear leucocytes.
Beta-adrenoceptor-mediated modulation of calcium-mediated stimulus-response coupling was studied using calcium ionophore (A23187) activation of polymorphonuclear leucocytes (PMNL). Oxygen metabolite generation was measured with luminol- and lucigenin-dependent chemiluminescence in both whole blood and isolated PMNL. Isoprenaline reduced PMNL response by 53% in a dose-dependent fashion. The effect was saturable, stereoselective, antagonized by propranolol and significant at isoprenaline concentrations as low as 0.01 nM. Fifty % maximal response was induced by 0.26 nM, 3 nM, and 125 nM isoprenaline, adrenaline and noradrenaline respectively. Because the effects of beta-adrenoceptor agonists in PMNL have not consistently correlated with measurements of cyclic AMP, alternative means of increasing cyclic AMP were studied. Forskolin and dibutyryl cyclic AMP inhibited PMNL with significant effects at 1.0 microM and 10 microM respectively. The effects of beta-adrenoceptor agonists were much greater when PMNL were activated by calcium ionophore compared with opsonized zymosan. Isoprenaline had no effect upon 1-oleoyl-2-acetylglycerol activated PMNL. Because catecholamine modulation of oxygen metabolite generation can be characterized pharmacologically, PMNL activation by calcium ionophore is an excellent model for study of beta-adrenoceptor function in viable human cells. In contrast to previously described beta-adrenoceptor agonist modulation of PMNL function, inhibition of calcium-mediated activation is significant at physiological concentrations. The clinical consequences of such catecholamine effects are dependent upon the mechanism of PMNL activation in a specific circumstance.
Mack
J A
JA
Nielson
C P
CP
Stevens
D L
DL
Vestal
R E
RE
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008163:Luminescent Measurements; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D000001:Calcimycin; D003994:Bucladesine; D011433:Propranolol; D007545:Isoproterenol