Drug modification of catecholamine synthesis and uptake in early chick embryos

Abstract

Using fluorescence histochemistry for catecholamines, the primary trunks in the chick embryo can be seen on the third day of development. It has been reported previously that the enzymes necessary for production of epinephrine and norepinephrine are not present until after the third day of incubation, and that the yolk contains both of these catecholamines. Therefore, the source of catecholamines in the primary trunks has been studied using alpha-methyl-p-tyrosine (AMT) to block synthesis and desmethylimipramine (DMI) to block uptake. Only embryos treated with both AMT and DMI showed an absence of fluorescence in the primary trunks. However, radioisotopic-enzymatic measurements of catecholamines in whole embryos revealed that epinephrine and norepinephrine were depleted by AMT alone. This indicates that the catecholamines in the primary trunks are synthesized rather than taken up from the yolk. Depletion of the catecholamines in the primary trunks did not cause any developmental aberration in either the primary or secondary sympathetic trunks, which may indicate that catecholamines are not necessary for the development of the trunks, or may be attributed to alpha-methylnorepinephrine, which was present in AMT-treated embryos. Blocking uptake alone caused large increases in both epinephrine and norepinephrine. Since these increases were blocked by AMT, they are believed to be due to increased tyrosine hydroxylase activity. This may indicate that there is end-product regulation of tyrosine hydroxylase in the developing primary sympathetic trunks similar to that reported in adults.