Glucagon modulates superoxide generation in human polymorphonuclear leucocytes.
It has been found that leucocytes possess receptor sites for glucagon and glucagon was shown to increase during bacterial infection. To verify the interconnection between glucagon, leucocytes and bacterial infection we studied the effect of glucagon on superoxide generation and second messenger transduction in PMNs. We found that glucagon could not stimulate chemiluminescence by itself but it could enhance FMLP- but not PMA-induced chemiluminescence in a concentration (50-800 pg/ml) dependent manner. However, after incubation of PMNs with 10 microM of ST-638 (a tyrosine kinase inhibitor) the enhancement effect converted into inhibitory effect. We also found that glucagon treatment of PMNs increased both IP3 and cyclic AMP levels as second messengers. ST-638 greatly attenuated the IP3 increment in the glucagon-treated FMLP-stimulated PMNs. From these results we can conclude that glucagon could enhance superoxide generation from FMLP-stimulated PMNs by elevating IP3. Inhibition of IP3 increment by tyrosine kinase blockade uncover the inhibitory effect of the increasing cyclic AMP on superoxide production.
Al-essa
L
L
Department of Pharmacology, Gifu University School of Medicine, Japan.
Niwa
M
M
Kobayashi
M
M
Nozaki
M
M
Tsurumi
K
K
D002934:Cinnamates / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005934:Glucagon / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D007093:Imidazoles; D007293:Inosine Triphosphate / Q000097:blood; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000502:physiology; D013440:Sulfides / Q000494:pharmacology; D013481:Superoxides / Q000097:blood*
D002934:Cinnamates; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007093:Imidazoles; D013440:Sulfides; C060747:ST 638; D013481:Superoxides; D007293:Inosine Triphosphate; C080213:3,7-dihydro-6-(4-(2-(N'-(5-fluoresceinyl)thioureido)ethoxy)phenyl)-2-methylimidazo-(1,2-a)pyrazin-3-one; D009240:N-Formylmethionine Leucyl-Phenylalanine; D005934:Glucagon; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases