Abstract
From the bronchioles of guinea-pigs, preparations were isolated for registration of perfused pressure on electrical field stimulation (EFS) and by application of drugs. The perfused bronchioles contracted when EFS was applied in the presence of atropine and phentolamine suggesting a non-adrenergic non-cholinergic (NANC) response. (R)-alpha-Methylhistamine (methylhistamine), a selective H3 agonist, reduced the NANC bronchoconstrictor response in a concentration-dependent manner. beta-Adrenoceptors, muscarinic and histamine (H1 and H2 receptor) antagonists, epithelial removal and cyclooxygenase inhibition had no effect on this inhibitory action of methylhistamine whereas the H3 antagonist, thioperamide, reduced the inhibitory effect of methylhistamine with a Ki value of 2.98 x 10(-9) M. Methylhistamine had no effect on the concentration-dependent contraction induced by exogenous substance P and neurokinin A, demonstrating that an H3 receptor might inhibit the release of transmitter from NANC nerves on guinea-pig perfused bronchioles in-vitro.
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