Neutrophil beta-adrenergic receptor responses are potentiated by acute exposure to phorbol ester without changes in receptor distribution or coupling

Journal Article · Tue Jan 01 00:00:00 EST 1991 · Life Sciences; (United States)

DOI:https://doi.org/10.1016/0024-3205(91)90103-I· OSTI ID:5751594

Kilfeather, S A; Stein, M; O'Malley, K ^[1]

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1. Royal College of Surgeons, Dublin (Ireland)

Exposure to the phorbol ester, phorbol 12-myristate, 13-acetate for 10 minutes enhanced cyclic AMP accumulation in human neutrophils under basal conditions and in response to the beta-adrenergic receptor agonist isoproterenol (ISO, 1{mu}M) and the adenylate cyclase activator forskolin (FSK, 10mM). Potentiation of responses to ISO by PMA was dose-dependent between 0.1 and 100nM PMA. The diacylglycerol analogue, 1-oleoyl-2-actylgylcerol (OAG) (50 {mu}M) also elevated beta-receptor responses, but 4beta-phorbol (100nM), lacking the capacity to activate PMA, was ineffective. Short-term exposure to the peptide n-formylmethionine leucyl-phenylalanine (FMLP, 1 {mu}M) also elevated neutrophil cyclic AMP accumulation. All potentiating effects of PMA on cyclic AMP production were inhibited by the protein kinase inhibitor 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H{sub 7}). PMA had no apparent effect on beta-receptor agonist-affinity, distribution between cell-surface and internalized compartments, or the capacity of ISO to induce beta-receptor internalization. Responses to FSK or ISO in terms of fold-stimulation of basal cyclic AMP accumulation int he presence of PMA were not elevated by PMA.

• OSTI ID: 5751594
• Journal Information: Life Sciences; (United States), Vol. 49:10; ISSN 0024-3205
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMP
BIOSYNTHESIS
PHORBOL ESTERS
BIOLOGICAL EFFECTS
SYMPATHOMIMETICS
RECEPTORS
CYCLASES
DOSE-RESPONSE RELATIONSHIPS
ENZYME ACTIVITY
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LEUKOCYTES
LYASES
MAMMALS
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NUCLEOTIDES
ORGANIC COMPOUNDS
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