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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.
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