https://www.jbc.org/content/247/4/1106.full.pdf

Radioimmunoassay for Cyclic Nucleotides I. PREPARATION OF ANTIBODIES AND IODINATED CYCLIC NUCLEOTIDES

https://science.sciencemag.org/content/sci/177/4047/401.full.pdf

Studies on the mechanism of hormone action

The hypothesis that physiological and developmental regulatory mechanisms are similar has been presented. Well-known developmental systems chosen illustrate the capability of the model to suggest a simple mechanism underlying the effects on development of a diverse group of chemicals. This hypothesis might be applied to other systems including the induction of the lens, limb regeneration, and the induction of the head of hydra (124). 

I have proposed this hypothesis not only because it permits consideration of a complex and varied array of experimental observations as reflections of a simple basic biochemical mechanism, but because recent technical advances in instrumentation and methods allow it to be directly tested. The fluorescent antibody method for the cytochemical measurement of cyclic nucleotides provides a means for investigating changes in the concentrations of cyclic nucleotides in developing cells and could also be used to detect neurotransmitters in developing cells. Similarly, the scanning electron microscope in the emitted x-ray mode provides a method for measuring changes in the content and distribution of cations within developing cells. 

The hypothesis presented here suggests pleasing asceticism on the part of eukaryotes. It suggests that simple derivatives of metabolites, including neurotransmitters and cyclic nucleotides, are linked together as regulatory molecules throughout the eukaryotes. The neurotransmitters are suggested to have a more general role in information transmission in eukaryotes than is generally accepted. They are hypothesized to have progressed during evolution from being intracellular messengers to a role as intercellular messengers for the relatively slow communication of developmental informaton; and, finally, this process has culminated with their participation in the rapid intercellular communication mediated by nerves. The thought that the complex pictures of physiological regulation and of the construction of a complex multicellular organism like man might be painted with so few colors is quite satisfying.

https://science.sciencemag.org/content/sci/185/4156/1012.full.pdf

Chemical messengers in development: a hypothesis.

Less than two decades ago Sutherland and Rall (1958; Rall et al., 1957) discovered a heat stable factor now known as adenosine 3′,5′-monophosphate, which accumulated in particulate fractions of liver homogenates exposed to epinephrine. This factor activated the breakdown of glycogen by soluble cytoplasmic enzymes. Although epinephrine activates glycogenolysis in intact hepatocytes, the hormone has no such effect on the soluble enzymes. Sutherland and Rall (1960; Rall and Sutherland, 1958, 1961, 1962) proposed that epinephrine might trigger the glycogenolytic response of hepatocytes by activating the synthesis of this nucleotide (cyclic AMP) whose structure (Fig. 1) by then had been shown to contain a unique cyclic phosphate bond (Lipkin et al., 1959). The polypeptide hormone glucagon also triggers the glycogenolytic response of liver, and activates the synthesis of cyclic AMP. From these and related observations on the actions of other hormones, the concept arose that cyclic AMP functioned as an intracellular “second messenger”, synthesized in response to certain hormones and which, by activating the appropriate sequence of enzymes, produced the specific biologic response of the target cell to the hormone (Sutherland et al., 1965).

The role of cyclic nucleotides in central synaptic function.

Radioimmunoassay for cyclic nucleotides. 3. Effect of ischemia, changes during development and regional distribution of adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in mouse brain.

The level of endogenous cyclic AMP in the rat brain in vivo began to increase markedly between the third and sixth days after birth, as did the ability of norepinephrine to stimulate the formation of cyclic AMP in brain tissue in vitro. Adenyl cyclase activity in broken cell preparations, when measure in the absence of sodium fluoride, increased with age up to a point, but began to decline between the fifth and ninth days postpartum. Activity continued to increase when measured in the presence of fluoride, suggesting that the apparent stimulatory effect of this ion may in fact be the reversal of an inhibitory influence which is absent or almost absent at birth. Cyclase activity at all ages was restricted to particulate matter, whereas apparent phosphodiesterase activity was present in particulate as well as soluble fractions. The catabolic system for cyclic AMP developed in a similar manner in both fractions. Theophylline produced the same degree of inhibition of this system at all ages.

E. C. Palmer

Papers

Cyclic AMP and adenyl cyclase in the developing rat brain.