S. A. Nelemans

Insulin induces airway smooth muscle contraction

Recently, the use of inhaled insulin formulations for the treatment of type I and type II diabetes has been approved in Europe and in the United States. For regular use, it is critical that airway function remains unimpaired in response to insulin exposure.

Induction of Na+/K(+)-ATPase activity by long-term stimulation of nicotinic acetylcholine receptors in C2C12 myotubes.

1 To investigate the role of long‐term stimulation of nicotinic acetylcholine receptors (AChRs) on the regulation of membrane potential, non‐contracting C2C12 myotubes were stimulated for 1–4 days with carbachol (10 μm) and membrane potentials were measured by the intracellular microelectrode technique after washing out of the drug. 2 The membrane potential (– 45.7 mV) gradually increased by 10.1 mV to − 55.8 mV during 4 days treatment, which was caused by enhanced electrogenic Na+/K+‐pumping. 3 The concentration‐dependent enhancement of Na+/K+‐ATPase activity in long‐term carbachol‐treated myotubes (4 days, EC50 = 5.3 μm) was prevented by co‐treatment with the competitive nicotinic AChR antagonist, pancuronium but not by the muscarinic antagonist, atropine. 4 Enhanced Na+/K+‐ATPase activity still developed in carbachol‐stimulated myotubes during cotreatment (4 days) with the nicotinic AChR‐channel blocker, chlorpromazine (1 μm). Membrane depolarization as such, obtained by incubation in high K+ medium (40 mm, 4 days) did not enhance Na+/K+‐ATPase activity. 5 Non‐treated myotubes possessed a high‐affinity ouabain binding site (Kd = 119 nm) in association with the low Na+/K+‐pumping activity. Long‐term stimulation of myotubes (4 days) with carbachol or with a combination of carbachol and chlorpromazine was accompanied by the development of an additional low‐affinity ouabain binding site (Kd = 13 μm). 6 Binding of monoclonal antibodies directed against either α1‐ or α2‐subunit of Na+/K+‐ATPase were both increased in myotubes treated with carbachol (4 days). 7 These results support the concept that nicotinic AChRs regulate Na+/K+‐ATPase activity, independent of the functionality of the receptor‐operated ion‐channel.