Indirect muscarinic receptor activation by pentamidine on airway smooth muscle

British Journal of Pharmacology
K BiyahC Advenier

Abstract

1. Pentamidine is routinely used to reduce the incidence of Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus, but it has been described as inducing pulmonary adverse effects, such as cough and bronchospasm. 2. In this paper we have investigated the effects of pentamidine on guinea-pig isolated main bronchi and human isolated bronchi. Pentamidine induced a concentration-dependent contraction in both preparations with pD2 values of 9.64 +/- 0.07 (n = 8) and 9.73 +/- 0.06 (n = 8) and a maximal effect (Emax) of 40 +/- 4% and 34 +/- 5% of the response to acetylcholine (1 mM) in guinea-pig and human bronchi respectively. Atropine (0.01 to 0.1 microM) and the muscarinic M3 receptor antagonist, hexahydro-siladiphenidol (0.1 and 1 microM) inhibited pentamidine-induced concentration-responses in both preparations in a non-competitive manner, whereas only high concentrations of the M1 receptor antagonist pirenzipine (1 microM) inhibited pentamidine concentration-response curves. 3. The cholinesterase inhibitor, tacrine (1 microM), potentiated the effect of pentamidine; in contrast, morphine inhibited pentamidine-induced responses. 4. The bronchoconstrictor effect of pentamidine on guinea-pig and human ...Continue Reading

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Citations

Jul 23, 2013·European Journal of Medicinal Chemistry·Donald A PatrickRichard R Tidwell
Jun 26, 2013·Journal of Medicinal Chemistry·Donald A PatrickRichard R Tidwell
Oct 12, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Benjamin SarriaEsteban J Morcillo
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Feb 24, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·John T FisherJürgen Wess
May 11, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jörg W WegenerFranz Hofmann
Oct 5, 2012·Acta Physiologica·P OchodnickyM C Michel
Jan 2, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Matthias SausbierPeter Ruth
Jul 4, 2013·Molecular Endocrinology·Kenichiro NakajimaJürgen Wess
Jun 17, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Bernard T DrummKenton M Sanders
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