Histaminic bronchospasm potentiated by adenosine: investigation of the mechanisms.
In anaesthetized guinea pigs, adenosine enhances the histamine-induced bronchospasm by means of a mechanism partly involving non-adrenergic-non-cholinergic (NANC) nerves, not related to capsaicin-sensitive neurons (Breschi et al., 1994). In the present paper, we excluded any interference by adenosine with the mediators known to be present in the airway inhibitory NANC system, VIP (vasoactive intestinal polypeptide) and NO (nitric oxide). The use of alpha-chymotrypsin or L-N(G)-nitro-arginine methyl ester (L-NAME) failed to modify the potentiation under study. The effects of adenosine were further investigated by studying whether an increased release of excitatory mediators from non-neural cells, in particular 5-HT (5-hydroxytryptamine, serotonin) and arachidonic products, was involved. In this connection, methysergide did not significantly affect the modulatory action of adenosine, revealing that the release of 5-HT was also not involved. Inhibition was obtained with hydrocortisone and with nordihydroguaiaretic acid, but not with indomethacin or with the mastocyte membrane stabilizer, sodium cromoglycate. This evidence suggests that lipooxygenase products, not derived from mastocytes, probably participate in the potentiating effect of adenosine.
Nieri
P
P
Institute of Biological Sciences, Faculty of Pharmacy, University of Pisa, Italy.
Lazzeri
N
N
Martinotti
E
E
Breschi
M C
MC
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology; D001986:Bronchial Spasm / Q000139:chemically induced* / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011999:Recruitment, Neurophysiological / Q000187:drug effects; D012137:Respiratory System / Q000187:drug effects / Q000294:innervation; D012701:Serotonin / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000502:physiology
D001095:Arachidonic Acids; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D012701:Serotonin; D014660:Vasoactive Intestinal Peptide; D006632:Histamine; D019001:Nitric Oxide Synthase; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester