The influence of chronic antidepressant administration on expression of the three major phosphodiesterase (PDE) 4 subtypes found in brain (PDE4A, PDE4B, and PDE4D) was examined. The treatments tested included representatives of four major classes of antidepressants: selective reuptake inhibitors of serotonin (sertraline and fluoxetine) or norepinephrine (desipramine), a monoamine oxidase inhibitor (tranylcypromine), and electroconvulsive seizure. Expression of PDE4A and PDE4B, but not PDE4D, mRNA and immunoreactivity were significantly increased in rat frontal cortex by chronic administration of each of the four classes of antidepressants. We also found that antidepressant administration significantly increased the expression of PDE4B mRNA in the nucleus accumbens, a brain region thought to mediate pleasure and reward that could also contribute to the anhedonia often observed in depressed patients. In contrast, expression of PDE4A and PDE4B were not influenced by short-term treatment (1 or 7 d) and were not influenced by chronic administration of nonantidepressant psychotropic drugs (cocaine or haloperidol), demonstrating the time dependence and pharmacological specificity of these effects. Upregulation of PDE4A and PDE4B may represent a compensatory response to antidepressant treatment and activation of the cAMP system. The possibility that targeted inhibition of these PDE4 subtypes may produce an antidepressant effect is discussed.

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The gene, penPC, for fi-lactamase I of Bacillus cereus 569/H has been cloned and its expression studied in Escherichia coli. The protein product from the in vitro translation of penPC was shown by gel electrophoresis to have an Mr of 36000 which is larger than the in vivo products found in B. cereus and E. coii. The DNA sequence of the signal region was determined. It revealed that the smallest known mature form present in B. cereus culture fluids is preceded by 45-48 amino acids in pre-&lactamase I, considering that there are 3 initiation codons in the same reading frame, one or more of which might be initiating translation. Unlike the Bacillus licheniformis 749/C fl-lactamase, which has a membrane-bound thioether lipoprotein form, the single Cys residue in the B. cereus ,&lactamase I signal sequence is unmodified and a single processed form of the enzyme is present in E. coli cells carrying penPC.