The Point of Action of Adrenin in Muscle
From the evidence presented in the foregoing pages it is clear that adrenin somehow is able to bring about a rapid recovery of normal irritability of muscle after the irritability has been much lessened by fatigue, and that the higher contractions of a fatigued muscle after an injection of adrenin are due, certainly in part, to some specific action of this substance and not wholly to its influence on the circulation. Some of the earlier investigators of adrenal function, notably Albanese,[4] and also Abelous and Langlois,[5] inferred from experiments on the removal of the glands that the rôle they played in the bodily economy was that of neutralizing, destroying or transforming toxic substances produced in the organism as a result of muscular or nervous work. It seemed possible that the metabolites might have a checking or blocking influence at the junction of the nerve fibres with the muscle fibres, and might thus, like curare, lessen the efficiency of the nerve impulses. Radwánska’s observation[6] that the beneficial action of adrenin is far greater when the muscle is stimulated through its nerve than when stimulated directly, and Panella’s discovery[7] that adrenin antagonizes the effect of curare, were favorable to the view that adrenin improves the contraction of fatigued muscle by lessening or removing a block established by accumulated metabolites.
The high threshold of fatigued denervated muscle, however, Gruber found was quite as promptly lowered by adrenin as was that of normal muscles stimulated through their nerves. [Fig. 23] shows that the height of contraction, also, of the fatigued muscle is increased when adrenin is administered. In this experiment the left tibialis anticus muscle was stimulated directly by thrusting platinum needle electrodes into it. The peroneus communis nerve supplying the muscle had been cut and two centimeters of it removed nine days previous to the experiment. The rate of stimulation was 120 times per minute and the initial tension of the spring about 120 grams. At the point indicated by the arrow an injection of 0.1 cubic centimeter of adrenin (1:100,000) was made into a jugular vein. A fall in arterial pressure from 110 to 86 millimeters of mercury and a simultaneous betterment of 20 per cent in the height of contraction were obtained. It required four minutes of fatigue (about 480 contractions) to restore the muscle curve to its former level. Results similar to this were obtained from animals in which the nerve had been cut 7, 9, 12, 14, and 21 days. In all instances the nerve was inexcitable to strong faradic stimulation.
Figure 23.—Top record, blood pressure with mercury manometer. Middle record, contractions of a denervated muscle (tibialis anticus) 240 per minute against a spring having an initial tension of 120 grams (peroneus communis nerve was cut nine days before this record was taken). Bottom record (zero blood pressure), time in half minutes. At the point indicated by an arrow 0.1 cubic centimeter of adrenin (1:100,000) was injected intravenously.
In Radwánska’s experiments, mentioned above, the muscle was stimulated directly when the nerve endings were intact. It seems reasonable to suppose, therefore, that in all cases he was stimulating nerve tissue. Since a muscle is more irritable when stimulated through its nerve than when stimulated directly (nerve and muscle), a slight change in the irritability of the muscle by adrenin would naturally result in a greater contraction when the nerve was stimulated. Panella’s results also are not inconsistent with the interpretation that the effect of adrenin is on the muscle substance rather than on the nerve endings. A method which has long been used to separate muscle from nerve is that of blocking the nervous impulses by the drug curare. Gruber found that when curare is injected the threshold of the normal muscle is increased as was to be expected from the removal of the highly efficient nervous stimulations. And also, as was to be expected on that basis, curare did not increase the threshold in a muscle in which the nerve endings had degenerated. Adrenin antagonizes curare with great promptness, decreasing the heightened threshold of a curarized muscle, in five minutes or less, in some cases to normal. From this observation it might be supposed that curare and fatigue had the same effect, and that adrenin had the single action of opposing that effect. But fatigue raises the threshold of a curarized muscle, and adrenin then antagonizes this fatigue. Langley[8] has argued that curare acts upon a hypothetical “receptive substance” in muscle. If so, probably curare acts upon a substance, or at a point, different from that upon which fatigue acts; for, as the foregoing evidence shows, fatigue increases the threshold of a muscle whether deprived of its nerve supply by nerve section and degeneration or by curare, whereas curare affects only the threshold of a muscle in which the nerve endings are normal.[9] And since adrenin can oppose the effects of both curare and fatigue, it may be said to have two actions, or to act on two different substances or at two different points in the muscle.
The evidence adduced in the last chapter indicated that the greater “head” of arterial pressure produced by the more rapid heart beat and the stronger contraction of many arterioles in times of great excitement would be highly serviceable to the organism in any extensive muscular activity which the excitement might involve. By assuring an abundant flow of blood through the enlarged vessels of the working muscle, the waste products resulting from the wear and tear in contraction would be promptly swept away and thus would be prevented from impairing the muscular efficiency. The adrenin discharge at such times would, as was pointed out, probably reënforce the effects of sympathetic impulses. The evidence presented in this chapter shows that adrenin has also another action, a very remarkable action, that of restoring to a muscle its original ability to respond to stimulation, after that has been largely lost by continued activity through a long period. What rest will do only after an hour or more, adrenin will do in five minutes or less. The bearing of this striking phenomenon on the functions of the organism in times of great need for muscular activity will be considered in a later discussion.