Effects of terbutaline on NGF formation in allergic inflammation of the rat.
1. The aim of this study was to determine the effects of the beta adrenergic agonist terbutaline on NGF increase caused by allergic inflammation in rats. 2. Intraplantar antigen injection in sensitized rats increased paw volume and stimulated NGF biosynthesis in the skin of the injected paw as determined 3 and 6 h after injection. Treatment of rats with terbutaline (0.1 - 0.3 mg kg(-1), s.c.) had no significant effect on the NGF concentration in non-inflamed skin, but reduced oedema, and at 0.3 mg kg(-1) also NGF mRNA and immunoreactive NGF in the skin of the inflamed paw in a propranolol-reversible manner. In carrageenan-induced inflammation, terbutaline did not significantly reduce the inflammation-induced increase of NGF in paw skin. 3. Exposure of sensitized rats to aerosolized antigen (twice, 24 h interval) increased protein content, eosinophil leukocytes, and immunoreactive NGF in the bronchoalveolar lavage fluid (BAL, obtained 16 h after the second antigen exposure). Treatment of rats with terbutaline (0.3 mg kg(-1), s.c. 30 min before the second antigen challenge) suppressed antigen-induced elevation of protein and eosinophil leukocytes, and reduced the concentration of NGF in BAL to values similar to those found in non-sensitized rats. 4. The present results demonstrate anti-allergic properties of terbutaline in rats that were accompanied by a marked reduction of antigen-induced NGF increase in skin and BAL, respectively. These results are compatible with the assumption that terbutaline primarily suppressed the immune response to antigen thereby attenuating the release of vasoactive mediators and the stimulation of NGF biosynthesis.
Amann
R
R
Institute of Experimental & Clinical Pharmacology, University of Graz, Univ.-Platz 4, A-8010 Graz, Austria. rainer.amann@kfunigraz.ac.at
Peskar
B A
BA
Schuligoi
R
R
D000318:Adrenergic beta-Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000276:immunology; D018893:Bronchoalveolar Lavage; D004487:Edema / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004804:Eosinophils / Q000276:immunology; D006614:Hindlimb / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D020932:Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D011433:Propranolol / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013726:Terbutaline / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000941:Antigens; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D011433:Propranolol; D013726:Terbutaline