NOR-EPINEPHRINE[-(3,4-DIHYDROXYPHENYL)--HYDROXYETHYLAMINE] AS A POSSIBLE MEDIATOR IN THE SYMPATHETIC DIVISION OF THE AUTONOMIC NERVOUS SYSTEM

¹ From the Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee

1. In an effort to obtain some information concerning the chemical nature of "liver sympathin" ("sympathin E" of Cannon and Rosenblueth), we have compared directly, in the same animal, the responses evoked by injected dl-nor-epinephrine [-(3,4-dihydroxyphenyl)--hydroxyethylamine] and l-epinephrine with those induced by "liver sympathin" (stimulation of the hepatic nerves).

2. The responses of the following effector systems to these agents were studied in the cat, under dial (Ciba) anesthesia, with the vagi sectioned and the adrenals ablated:

a. Vasomotor system.

b. Vasomotor system after the administration of ergotoxine (or ergotamine).

c. Nictitating membrane (sensitized).

d. Uterus, non-pregnant and pregnant.

e. Iris.

f. Intestine.

3. It is concluded that the responses to dl-nor-epinephrine are strikingly similar to those induced by "liver sympathin."

4. Certain variations in the responses to nor-epinephrine and "liver sympathin" are considered and reasons suggested therefor.

5. The possible origin of nor-epinephrine in the body is discussed from a purely theoretical standpoint.

6. The responses, in vitro, of the isolated non-pregnant cat uterus, non-pregnant rat uterus, and rabbit intestine to l-epinephrine and dl-nor-epinephrine are considered.

7. Certain pharmacological properties of nor-epinephrine and epinephrine are compared and the generalization is made that the former has a greater intrinsic power of inducing contraction (in the effector systems studied) than the latter, but that epinephrine has a much greater intrinsic power of inducing relaxation. An apparent exception to this generalization, the response of the iris, is discussed and an explanation offered.

8. Theories of chemical mediation in the sympathetic division of the autonomic nervous system are discussed in the light of our own results as well as those of others.

9. It is suggested that the available experimental evidence indicates that:

a. There are at least two "adrenergic" mediators involved in the transmission of impulses from sympathetic nerves to effector cells.

b. Either agent may cause relaxation or contraction (depending upon the effector cell concerned), but that one of them (S_c) has a greater intrinsic power of inducing contraction but less intrinsic power of inducing relaxation than the other (S_r).

c. These agents (S_c and S_r), after their liberation at (or in the vicinity of) the nerve endings, may without further differentiation either affect cells locally or, if released in sufficient quantity, may diffuse into the blood stream and affect distant structures.

10. It is further suggested that if the tentative assumption is made that l-nor-epinephrine is S_c and l-epinephrine is S_r, a simple working hypothesis is afforded for explaining both local and remote "adrenergic" effects induced by the stimulation of postganglionic sympathetic fibers and renders unnecessary the postulation of the intervention of cellular constituents in order to account for two "sympathins."

This article has been cited by other articles:

				U. S. v. EULER Sympathin E and Nor-Adrenaline Science, April 23, 1948; 107(2782): 422 - 422. [PDF]

				M. L. TAINTER, B. F. TULLAR, and F. P. LUDUENA Levo-Arterenol Science, January 9, 1948; 107(2767): 39 - 40. [PDF]