Fly Agaric in Ireland and Muscarine as asthma treatment

Everyone is charmed when we chance upon our first Fly Agaric, the iconic red and white seat of many a storybook fairy or elf. Just then the sky darkens, the mother and father of all downpours leaving no shelter. Waterproofs are useless, we can only head back to the hotel?
Go to: Muscarinic receptors in the lung In the lungs, anticholinergic compounds block muscarinic receptors on airway smooth muscle, glands and nerves to prevent muscle contraction, gland secretion and enhance neurotransmitter release. There are five muscarinic receptor subtypes [designated M1 through M5 by the IUPHAR (Caulfield and Birdsall, 1998)] all belonging to the large family of seven transmembrane G-protein coupled receptors. In human lung (and in all animal species tested), acetylcholine induces bronchoconstriction by stimulating M3 (Figure 1) receptors on smooth muscle (Roffel et al., 1990). Although airway smooth muscle contraction is mediated by M3 receptors, the majority of muscarinic receptors on airway smooth muscle are actually M2 (Barnes, 1993). These M2 receptors contribute indirectly to airway smooth muscle contraction by limiting β-adrenoceptor-medicated relaxation through inhibition of adenylate cyclase (Fernandes et al., 1992). Glandular secretion is also mediated predominantly by M3 muscarinic receptors on submucosal cells (Marin et al., 1976; Borson et al., 1980; Phillips et al., 2002). Figure 1 Muscarinic receptors in lungs. Muscarinic receptors (MR) are present throughout the lungs and control smooth muscle contraction, gland secretion, acetylcholine (ACh) release from parasympathetic nerves and probably also inflammatory cells. Only receptors (more ...) Muscarinic receptors are also present on parasympathetic nerves supplying the lungs (Fryer and Maclagan, 1984). M2 muscarinic receptors on postganglionic parasympathetic nerves (Faulkner et al., 1986; Fryer et al., 1996) limit acetylcholine release, thus providing a physiologically relevant, negative feedback control over acetylcholine release (Fryer and Maclagan, 1984; Baker et al., 1992). Blocking M2 receptors with mmuscarinic antagonists including atropine and ipratropium or using selective M2 receptor antagonists such as gallamine, significantly potentiates vagally induced bronchoconstriction (Fryer and Maclagan, 1984; 1987; Blaber et al., 1985; Faulkner et al., 1986). Neuronal M2 receptors are vulnerable, and thus their function is significantly decreased after respiratory viral infection, antigen challenge, or exposure to organophosphates or ozone (Empey et al., 1976; Aquilina et al., 1980; Fryer and Jacoby, 1991; Schultheis, 1992; Schultheis et al., 1994; Sorkness et al., 1994). They are also less functional in humans with asthma (Minette et al., 1989). Decreased function of the neuronal M2 receptors is mediated by various mechanisms including blockade by endogenous antagonists and down-regulation of receptor expression. The resulting increase in acetylcholine release is thought to be an important mechanism of airway hyperreactivity. Clinically, anticholinergic drugs are used as bronchodilators in combination with anti-inflammatory steroids in the treatment of asthma and chronic obstructive pulmonary disease (COPD). Asthma is characterized by variable airflow limitation that is partially reversible spontaneously or with treatment. Underlying this airflow limitation is chronic inflammation that increases airway hyperresponsiveness to various stimuli (EPR-3, 2007). COPD is characterized by chronic airflow limitation that is not fully reversible. Patients with COPD can experience acute worsening in symptoms. These exacerbations are characterized by increased sputum production and shortness of breath (Rabe et al., 2007). COPD and asthma symptoms overlap; however, the most distinguishing difference between conditions is airflow limitation reversibility. This review covers the history of clinically relevant anticholinergic drugs in asthma and COPD.