Bronchodilatation of guinea-pig perfused bronchioles induced by the H3-receptor for histamine: role of epithelium.
1. The influence of epithelium on the effects of H3-histamine receptor agonist (R)alpha-methylhistamine [(R)alpha-MeHist] on airways was investigated on the guinea-pig perfused bronchioles. 2. In preparations under resting tone, removal of the bronchiolar epithelium or treatment with the cyclo-oxygenase inhibitor indomethacin (10(-5) M) increased the constriction induced by histamine and acetylcholine in a concentration-dependent manner without an alteration of the K(+)-induced contraction. 3. In this preparation (R)alpha-MeHist induced a concentration-dependent bronchodilatation which was antagonized in a competitive manner by thioperamide (an H3-antagonist) with a pA2 value of 8.6. 4. This bronchodilatation was reversed to a low concentration-dependent constriction after either removal of the epithelium or treatment with indomethacin (10(-5) M) but was unaffected by both 10(-5) M tranylcypromine (an inhibitor of PGI2 synthesis) and 5 x 10(-5) M NG-nitro-L-arginine methyl ester (an inhibitor of NO synthesis). 5. It is suggested that, in guinea-pig perfused bronchioles (R)alpha-MeHist induces an epithelium-dependent relaxation via the release of metabolite(s) of arachidonic acid.
Burgaud
J L
JL
Laboratoire de Pharmacologie, UFR de Pharmacie, Limoges, France.
Oudart
N
N
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D004848:Epithelium / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology*; D006633:Histamine Antagonists; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D010208:Papaverine / Q000494:pharmacology; D010477:Perfusion; D010880:Piperidines / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology; D018100:Receptors, Histamine H3 / Q000187:drug effects / Q000502:physiology*; D014191:Tranylcypromine / Q000494:pharmacology
D000927:Anticonvulsants; D001993:Bronchodilator Agents; D017442:Histamine Agonists; D006633:Histamine Antagonists; D008761:Methylhistamines; D010880:Piperidines; D011453:Prostaglandins; D018100:Receptors, Histamine H3; D014191:Tranylcypromine; C069357:alpha-methylhistamine; D006632:Histamine; D001120:Arginine; D010208:Papaverine; C052075:thioperamide; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin