Responses of isolated bronchial muscle to ganglionically active drugs / by D.F. Hawkins and W.D.M. Paton.

  • Hawkins, D. F. (Denis Frank)
Date:
[1958?]
Catalogue details

Licence: In copyright

Credit: Responses of isolated bronchial muscle to ganglionically active drugs / by D.F. Hawkins and W.D.M. Paton. Source: Wellcome Collection.

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    ganglion cells of the lung (Larsell & Mason, 1921) the question arises whether these ganglion cells play a part in mediating both types of vagal action, or whether their function is solely bronchoconstrictor. The present work was designed to study the characteristics of the ganglionic tissue within the trachea and large bronchi, using isolated preparations of trachea and bronchi from guinea-pig and cat. Pharmacological evidence will be presented that at least two types of ganglion cell, adrenergic and cholin¬ ergic, are present in these tissues. METHODS Material. Guinea-pig tracheae and bronchi were obtained from animals freshly stunned and bled out. Cat trachea was taken from animals which had been anaesthetized with ether for other purposes; large bronchi from these animals were taken at the end of experiments under ether or chloralose anaesthesia, lasting for 2-3 hr. We are grateful to Professor R. S. Pilcher for two human lungs, each removed at pneumonectomy for carcinoma in one lobe. Isolated 'preparations. Chains of rings cut from bronchi and trachea, of the type described by Epstein (1932) and Castillo & de Beer (1947) were employed. Bronchi from guinea-pigs, cats, and humans were dissected free from lung tissue, and tied in chains with loops of cotton. Rings cut from guinea-pig trachea were orientated alternately and tied tightly with cotton so that the muscle strips were aligned. With cat trachea and the larger human bronchi single rings were often adequate. Rings cut by sectioning the trachea at intervals of 8-10 mm, containing two or three cartilaginous rings, were sometimes used; these were suspended by means of stitches put into the walls with a small curved needle. The preparations were suspended in isolated organ baths, and the tonus level recorded with light balsa-wood frontal-writing levers recording on a lightly smoked drum, rotating at 1 mm/min. The solution used was Krebs-Henseleit solution: composition (g/1.), NaCl 6-87, KC1 0-42, CaCl2 0*28, MgS04.7H20 0-29, NaH2P04.2H20 0C8, NaHC03 2C0, glucose 1-00, aerated with oxygen and 5 % C02 at 37° C. The bath volume was 50 ml. The preparations were usually set up within 1 hr of removal from the animal, and then left for a further hour before testing. With guinea-pig trachea chains a marked rise in tone occurred during this time. The preparations responded to drugs for 10-12 hr. A special difficulty sometimes arose from the relatively high tone of the preparation of guinea-pig tracheal muscle. Not in¬ frequently, washing out the bath led to a considerable change of tone, commonly a reduction, followed by a return to normal over a period of 10-20 min. In the absence of washing out only slow drifts of tone occurred, and there was no difficulty in distinguishing them from bronchocon¬ strictor or bronchodilator responses. The Ringer’s solution used by Epstein (1932) proved to be unsatisfactory. Preparations of guinea-pig trachea immersed in it were insensitive and soon ceased to respond to drugs at all. Drugs. Drug concentrations were expressed in terms of the whole salt unless the contrary is stated. For the pA2 determinations molar concentrations were computed in terms of C33H3705N5, CH3S03H for dihydroergotamine methanesulphonate and of C33H3505N5.^(C4H606) for ergot- amine tartrate. The drugs used were: acetylcholine iodide, anagyrine hydriodide, ascorbic acid, atropine sulphate, barium chloride, Bj^-pyrimidine hydrochloride (2-methyl-4-amino-5-methylamine pyrimidine; Roche Products), choline chloride, coniine hydrochloride, cytisine perchlorate, di- benamine hydrochloride, dibenzyline hydrochloride (Smith, Kline and French Laboratories, Ltd.), dihydroergotamine methanesulphonate, egg albumin (flake), ergometrine maleate, ergotamine tartrate, ergotoxine ethanesulphonate, hexamethonium bromide, histamine dihydrogen phos¬ phate, L-adrenaline base, l-noradrenaline bitartrate monohydrate (Bayer Products, Ltd.), lobeline hydrochloride (Sandoz Products), mepyramine acid maleate (May and Baker, Ltd.),