A Correlation Between Inhibition of the Uptake Of³h From (±)‐³h‐noradrenaline and Potentiation of the Responses to (–)‐noradrenaline in the Guinea‐pig Isolated Trachea

Foster (1967) has recently speculated that the guinea-pig tracheal chain might be a suitable isolated tissue in which to seek a correlation between inhibition of uptake and potentiation of the effects of noradrenaline.This was suggested because a variety of drugs caused a concentration and time-dependent potentiation up to a very large dose- ratio (about 46).Cooling also caused a graded potentiation.The uptake of 3H from (± )-3H-noradrenaline has now been measured in the guinea-pig isolated trachea and the effects of desipramine, cocaine, phentolamine, (± )-metanephrine, guanethidine, phenoxybenzamine and cooling on this uptake assessed.The results of this assessment have been correlated with the previously reported potentiation of the action of (-)-noradrenaline caused by these procedures. METHODSThe Krebs solution, drugs and guinea-pigs used were as described by Foster (1967). Preparation of the trachea and method of incubationA guinea-pig was stunned and exsanguinated.The whole trachea was removed and opened with scissors by an anterior midline cut.It was then divided into four or five equal fragments by trans- verse cuts.These fragments were strung loosely together on a short length of Terylene thread by piercing one cartilage plate of each.This thread was then tied into a loop which was attached to the end of a polyethylene bubbling tube transmitting 95% oxygen and 5% carbon dioxide from a manifold.A rack with positions for twelve test tubes was mounted in a water bath at 37.50 C so that six tracheae could be handled at once.A test tube containing 10 ml. of Krebs solution was placed in this rack and the bubbling tube, and attached trachea, plunged into it.When it was necessary to change the bathing fluid, the bubbling tube with its attached trachea was lifted from the test tube and transferred to one containing fresh solution, which had been positioned 1 min before.The interval between making the preparation and exposing it to a radioactive solution was never less than 45 min and the Krebs solution was changed at least-every'30'min' up to this time.