Effects of Noradrenaline on the activation and the stability of brain adenylate Cyclase

This is the letter send to Washington Post in Oct. 23, 2004.This is the letter send to Washington Post in Oct. 23, 2004.

Dr. Alfred Bennun
Full Professor of Biochemistry
Rutgers, The State University

REF.: Article ´Is Every Memory Worth Keeping?´
by Rob Stein., Tuesday, October 19, 2004; Page A01

Editorial Office Washington Post
23th, October2004

Dear Sirs,
In reference to the above article I am providing your Editorial Office with the pertinent information to the mechanism of action of the Beta-Blocker Propranolol over
the pharmacological Norepinephrine/Noradrenaline Receptor and emotional-memory which are inter-related to the activity of the enzyme Noradrenaline-activated Adenylate Cyclase.
At my laboratory in Rutgers University, I directed the work of Susan Brydon-Golz and Heripsime Ohanian for their Ph.D. This work resulted in the finding of a neurotransmitter-activated enzyme capable to participate in a molecular pathway for emotional-memory formation which was published as: ´Effects of Noradrenaline on the Activation and the Stability of Brain Adenylate Cyclase´, Biochemical Journal (1977) 166, 473-483.
When the article was accepted for publication the editors of Biochemical Journal asked me to cut from the discussion my perspective of the physiological and pharmacological role of the enzyme. Since, later is better than never, I am enclosing not only the citation mentioned above but also an illustration. This one provides information on the molecular pathway involving the adrenaline/epinephrine-activated enzyme. The activation of this enzyme leads to a cyclic AMP-dependent phosphorylation pathway changing the state of activation and/or deactivation of other enzymes which are involved in control of brain cells response.
If you read the article, Figure 1 shows increasing cyclic- AMP formation by Noradrenaline activation and inhibition by calcium. The later is known to enter into brain cells at the termination of a neurotransmitter-mediated impulse. Accordingly, the activation of the enzyme could be characterized to the general public as the initial step in memory formation. Since, there is a short-term memory, an intermediate-memory and a long-term memory, Propranolol, a beta-blocker, if given before long-term memory formation it will decrease and/or blurr its emotional content.
Figure 4 and 5 shows that if the enzyme was pre-incubated in a test tube with Noradrenaline for a long period of time, the enzyme becomes more labile and when assay for Noradrenaline-activation it shows that has become inactivated. On the other hand, Table 1 shows that if the enzyme was only pre-incubated with buffer, thereafter during its assay for Noradrenaline-activation, still remains active. For the general public it could be mentioned that an enzyme activated in the test tube by epinephrine, will make an investigator to expect that the same enzyme will function in physiological experiments as epinephrine-mediated emotions pathway for memory formation. To mediated emotions, (not only in brains but also in other tissues), is associated with the responses of the mind or psyches.
The same enzyme is also destroy for long exposure to epinephrine in the test tube or, in physiological correspondence, destroy by prolonged emotional responses. In other words since the enzyme molecules are part of the soma or body, when this enzyme is destroyed by overexposure to Noradrenaline is similar to be destroyed by the mind. Accordingly, this enzyme is the molecular connection between mind and body or the site for the psychosomatic response.
The connection between mind/psyches increasing secretion of epinephrine which in first instance stimulates the enzyme but later on by prolonged exposures to it destroys the enzyme/soma are the basis for psychosomatic diseases.
This, also corresponds to the observed pattern of progress of psychosomatic diseases which is first an hyperfunction follow by an hypofunction. Applying for brain would be anxiety follow by depression for other tissues like thyroid, hyperthyroism follow by hypothyroism.

Dr. Alfred Bennun

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