title: Autoregulation of acetylcholine release from vagus nerve terminals through activation of muscarinic receptors in the dog trachea.
abstract: 1. The effects of pirenzepine and gallamine on the membrane and contractile properties of smooth muscle cells and on excitatory neuro-effector transmission in the dog trachea were investigated by means of microelectrode, double sucrose gap and tension recording methods. 2. Pirenzepine (10(-7) M) and gallamine (10(-5) M) had no effect on the resting membrane potential or the input resistance of the smooth muscle cells. 3. Pirenzepine (10(-10)-10(-9) M) and gallamine (10(-7) M) enhanced the amplitude of twitch contractions evoked by field stimulation in the combined presence of indomethacin (10(-5) M) and propranolol (10(-6) M). At higher concentrations pirenzepine (10(-8) M) inhibited the twitch contractions in a dose-dependent manner. Both pirenzepine and gallamine in doses over 10(-7) and 10(-5) M, respectively, reduced muscle tone. 4. Pirenzepine (10(-10)-10(-9) M) and gallamine (10(-7) M) enhanced the amplitude of excitatory junction potentials (e.j.ps) evoked by field stimulation (single or repetitive stimulation). However, a high concentration of pirenzepine (10(-8) M) reduced the amplitude of e.j.ps. In parallel with its action on e.j.ps, pirenzepine (over 10(-9) M) reduced the response of smooth muscle cells to acetylcholine (ACh), in a dose-dependent manner. Gallamine (5 X 10(-5) M) markedly enhanced the amplitude of e.j.ps but also reduced the response of muscle cells to ACh. 5. ACh (10(-10)-10(-9) M) inhibited twitch contractions evoked by field stimulation, with a slight increase of resting tension. 6. Gallamine enhanced the summation of e.j.ps during repetitive field stimulation at a high frequency (20 Hz), but was without effect on the depression phenomena of e.j.ps observed during double stimulus experiments at different time intervals (5-60 s). 7. These results indicate that both pirenzepine and gallamine have dual actions on pre- and post-junctional muscarinic receptors in dog tracheal tissue. At low concentrations both agents potentiate excitatory neuro-effector transmission, presumably due to enhancement of release of ACh from vagal nerve terminals through blockade of a negative auto-regulatory process activated by endogenous ACh. At higher concentrations, these agents inhibit the response of smooth muscle cells to ACh through post-junctional muscarinic receptors and relaxation of the muscle tissue occurs.
authors: Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors: Y
authors: Y
authors: Ito
authors: T
authors: T
authors: Yoshitomi
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D004285:Dogs; D005260:Female; D005703:Gallamine Triethiodide / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009411:Nerve Endings / Q000378:metabolism; D010890:Pirenzepine / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D014132:Trachea / Q000294:innervation* / Q000378:metabolism; D014630:Vagus Nerve / Q000378:metabolism*
chemical_list: D011976:Receptors, Muscarinic; D010890:Pirenzepine; D000109:Acetylcholine; D005703:Gallamine Triethiodide