The hypothesis advanced in this article requires further validation. Undoubtedly it will require modification as our knowledge of biochemical control increases. Nevertheless, it should prove useful in focusing attention on the apparent similarity in the response of a large number of specific cell types to particular stimuli. Emphasis has been placed on a few common and apparently key elements in these responses. It is recognized that other factors are undoubtedly involved. Specifically, the changes in membrane potentials indicate the likelihood of widespread changes in the properties of the cell membrane, for example, changes in Na(+) and K(+) transport and distribution. These aspects of cellular responses may eventually prove to be of equal or greater importance than those common aspects of the system already identified.

Cell Communication, Calcium Ion, and Cyclic Adenosine Monophosphate

Purification and Characterization of a Protein Inhibitor of Adenosine 3',5'-Monophosphate-dependent Protein Kinases

Purification and properties of rabbit skeletal muscle adenosine 3',5'-monophosphate-dependent protein kinases.

The analysis of the contributions to synaptic plasticity and memory of cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB has recruited the efforts of many laboratories all over the world. These are six key steps in the molecular biological delineation of short-term memory and its conversion to long-term memory for both implicit (procedural) and explicit (declarative) memory. I here first trace the background for the clinical and behavioral studies of implicit memory that made a molecular biology of memory storage possible, and then detail the discovery and early history of these six molecular steps and their roles in explicit memory.

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The molecular biology of memory: CAMP, PKA, CRE, CREB-1, CREB-2, and CPEB

The levels of guanosine 3′,5′-cyclic phosphate (cGMP) and adenosine 3′,5′-cyclic phosphate (cAMP) were measured in rat hearts after perfusion with acetylcholine to determine if parallel or independent changes occurred in the levels of these two cyclic nucleotides. It was found that after perfusion with the cholinergic agent tissue, cGMP levels increased as much as 140%. This was accompanied by no change or slight decreases in cardiac cAMP concentrations. The increases observed in cGMP levels were found to parallel the negative inotropic but not the negative chronotropic effects of acetylcholine. Perfusion with isoproterenol led to increases in the rate and force of cardiac contractility and a lowering of cGMP levels. It was concluded that the tissue concentrations of cGMP and cAMP in the perfused rat heart can vary independently and that these two tissue cyclic nucleotides probably do not share the same metabolic or functional role in this tissue.

J.D. Corbin

Papers

A cyclic AMP--stimulated protein kinase in adipose tissue.