Control of human airway smooth muscle: in vitro studies.
An in vitro study of neural and myogenic control of human tracheal smooth muscle was undertaken. Over 80% of these had active tension and 13% had phasic contractile activity. Tonic and phasic activities were not reversed by indomethacin, 5,8,11,14-eicosatetraynoic acid, methysergide, mepyramine, atropine, or tetrodotoxin (TTX) but were blocked by the calcium antagonist verapamil. In some quiescent strips, tonic and/or phasic activity was induced by exposure to potassium-conductance blockers such as 4-aminopyridine (4-AP) and tetraethylammonium chloride (TEA). Electrical (field) stimulation resulted in frequency-dependent biphasic responses: an initial atropine-sensitive cholinergic contraction followed by a nonadrenergic relaxation. This biphasic response to low stimulus parameters (less than 0.5 ms, less than 15 Hz) was blocked by TTX and scorpion venom and enhanced by 4-AP and TEA, consistent with a neural mechanism. Relaxation responses to longer pulse durations (0.5-1 ms) were not blocked by TTX despite abolition of contraction nor were they enhanced by 4-AP and TEA, suggesting a nonneural mechanism. ATP, adenosine, arachidonate metabolites, histamine, 5-hydroxytryptamine, neurotensin, or vasoactive intestinal polypeptide were ruled out as possible nonadrenergic mediators. The nature and physiological significance of the nonneural inhibitory response remains unknown.
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology; D001095:Arachidonic Acids / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology; D004558:Electric Stimulation; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D012143:Respiratory Physiological Phenomena; D012701:Serotonin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D000631:Aminopyridines; D001095:Arachidonic Acids; D010455:Peptides; D011687:Purines; D013757:Tetraethylammonium Compounds; D012701:Serotonin; D019789:Tetraethylammonium; D006632:Histamine; D015761:4-Aminopyridine; D004298:Dopamine; D009638:Norepinephrine