THE CHEMICAL MEDIATION OF AUTONOMIC NERVOUS IMPULSES AS EVIDENCED BY SUMMATION OF RESPONSES

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Abstract
The relations between the responses and the frequency of supramaximal stimulation of autonomic nerves were studied in the following cases: a single hair in the tail of the cat, the nictitating membrane (isometric and isotonic contractions), acceleration of the heart, isotonic contractions of the cat''s pregnant uterus, inhibition of the duodenum, the adrenal medulla, stimulation of the stomach, inhibition of the heart, and responses of the submaxillary gland. The shapes of the records of the muscular responses are exponentials. The formula for relaxation, y = ke -k/t, is also applicable to the rate of disappearance of the response of the submaxillary gland after stimulation. With the exception of medulliadrenal secretion, which is in a linear relation with the frequency, all the systems investigated obey a hyperbolic law: R = F/(k''[long dash]kF). The area of the contractions is obtained by integration of the corresponding formulae; it is comparable to the total amount of saliva secreted; there exists again a hyperbolic ratio between the contraction areas or the total amounts of saliva and the frequencies of stimulation. The following hypothesis is proposed: each nervous impulse liberates a quantal amount of a chemical mediator M. M combines with some substance H in the effector, M + H MH. The response is proportional to the concentration of MH, not all-or-none. Free M is destroyed locally, hence relaxation. Relaxation of smooth muscle is an active process, a "decontraction," comparable to the disappearance of the salivary flow after stimulation.

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