The last several years have seen a renaissance of interest in PDEs as modulators of second messenger function. Much of the renewed interest has come from the recognition that there are a large number of different cyclic nucleotide-specific PDE isozymes, that these isozymes are differentially expressed in individual cell types, that they are differentially regulated, and that they are specialized to serve specific functions in the cells in which they are expressed. Currently> 30 different isozymes are recognized. The realization that individual PDE isozymes are regulated in both positive and negative manners has high-lighted the pivotal role played by PDEs in mediating cross-talk between second messenger pathways. It has also provided a conceptual basis for understanding many of the distinctive cell type-specific differences in the amplitude and duration of cAMP and cGMP signals produced in response to stimulation of adenylyl and guanylyl cyclase. The concept of differentially expressed and regulated PDE isozymes also implies that mdividual PDEs are likely to be good targets for therapeutic intervention in diseases caused or regulated by cyclic nucleotide-modulated transduction mechanisms. Pharmaceutical in-terest in the area has been further sparked by the promise that different PDE isozymes having distinct sequences at regulatory and catalytic sites should allow the development of selective therapeutic agents that can target a specific cyclic nucleotide pool in a very limited number of cell types. This in turn holds great promise of being able to limit the toxic side effects of many of the first-generation, nonselective inhibitors developed in the 1960s and 1970s.

The recent ASPET Colloquium on Multiple Phosphodies-terases held in Newport Beach, CA, on April 22-23, 1994, and the two companion ASPET Symposia held over the next 2 days at the Experimental Biology Meetings in Anaheim, CA, brought together> 150 scientists having interests in this area. The Colloquium was the first in a series to be sponsored by ASPET on rapidly developing topics of interest to both academic and industry pharmacologists and biological scientists. It is the purpose of this report to briefly summarize some of the newer and more interesting information presented at these meetings. This report cannot begin to cover all of the information pre-