MICROSCOPY RESEARCH AND TECHNIQUE 40:433 (1998) Introduction to Adenylate Cyclase Adenylyl cyclase (AC) is an intimate part of the cyclic adenosine monophosphate (cAMP) second messenger system and is present throughout many tissues, where it plays a role in a large number of cellular activities. Historically, most research on the microscopical localization of AC has relied on the enzyme’s own activity, enhanced by activators, to precipitate heavy metal ions at the reactive site. Since 1989, when Krupinsky et al. elucidated the amino acid sequence and structure of AC isoform type I, at least eight other isoforms have had their structure determined. This has opened the way for an accurate localization of the AC protein and its genetic message using immunocytochemical and in situ hybridization techniques. The relative newness of commercially available antibodies and probes has meant that there are few published results using immunocytochemistry or in situ hybridization methods. This disparity between methods is reflected in the present collection of articles, with only two of the articles using immunocytochemical techniques. The diverseness of tissue and cell processes in which AC is involved is amply demonstrated in this issue, with articles involving embryology, electrophysiology, pathology, and normal and abnormal muscle contraction. Most reviews on the subject of AC have highlighted the many tissues and cellular structures that are associated with the enzyme. In this issue, the review article by Richards and Richards has taken a historical look at the histochemical technique and its associated problems, rather than where the enzyme is localized. One of the problems associated with the histochemical technique is that of the capture agent and in the article by Rechardt the use of cerium ions, a commonly used alternative to lead ions as the capture agent, is discussed in relation to the localization of second messenger system enzymes. Rechardt discusses some of the handicaps with the method and its use in localizing AC in nervous tissue. The diversity of tissues and situations in which the localization of AC is of importance is illustrated in the majority of articles in this issue. Farnesi et al. have examined AC’s role in the embryological development of Bufo bufo, highlighting the possible role of cAMP in cellular differentiation. Els and Butterworth used electrophysiology and the histochemical localization of AC in cultured renal cells to suggest that r 1998 WILEY-LISS, INC. the action of vasopressin on apical membranes is probably not via the AC-cAMP pathway. Mayer and colleagues demonstrate a decrease of AC in liver and cell culture as a result of neoplastic transformation and discuss the possible consequences of this reduction. Adenylyl cyclase’s intimate relationship with calcium ions is highlighted in the last three articles of this thematic collection. Substantial research has gone into the relationship between AC and calcium in cardiac muscle, as evidenced by Schulze and Buchwallow’s review. Yammoto et al.’s localization of AC in human cardiac biopsies corresponds with that of Schulze and Buchwallow in cardiac tissue from rats. Finally, AC’s relationship with calcium does not appear to be restricted to cardiac muscle, as demonstrated by the results in Richards et al.’s article, in which AC isoform VI is localized in normal human myometrium for the first time. The article by Richards et al. and that of Schulze and Buchwallow perhaps serve as pointers to the future direction of AC localization, with a tendency towards the localization of the protein, rather than the working site of the enzyme. As suitable immunocytochemical and in situ hybridization probes are now commercially available, perhaps we should be looking towards experiments that combine both the more established histochemical technique with immunocytochemistry and/or in situ techniques on the same specimen to confirm that the protein/genetic message and the working enzyme occur at the same site. It is possible that differences in the localization of these components may occur in disease states, during development, or following neoplastic change and if detected will lead to a greater understanding of these processes, which in turn may lead to novel treatments for pathological conditions. PETER D.G. RICHARDS, MSc, DipRMS, MIBiol, CBiol Pretoria University, South Africa REFERENCE Krupinski, J., Coussen, F., Bakalyar, H.A., Tang, W-J., Feinstein, P.G., Orth, K., Slaughter, C., Reed, R.A., and Gilman, A.G. (1989) Adenylyl cyclase amino acid sequence: Possible channel- or transporter-like structure. Science, 244:1558–1564.