Second Messengers and Cell Regulation 
guanylyl cyclase receptor is similar to the first 
ANP receptor within intracellular regions but is 
only 43 percent identical in the extracellular, 
ligand-binding region. It now appears that a pep- 
tide other than ANP regulates this receptor. 
We subsequently discovered the existence of a 
third guanylyl cyclase receptor. This receptor 
binds small peptides released from various bacte- 
ria that cause acute diarrhea. This form of diar- 
rhea (often referred to as traveler's diarrhea) is 
prevalent in infant humans and young domestic 
animals. The receptor has the same general fea- 
tures as the two receptors described above but 
has a markedly different amino acid sequence 
within the toxin-binding region. Whether a regu- 
latory molecule not of bacterial origin normally 
exists that binds to this receptor is not yet known. 
During the past year, we have obtained evi- 
dence to suggest that at least two other guanylyl 
cyclase receptors exist. The hormones that nor- 
mally regulate these receptors have not yet been 
identified. It seems, therefore, that different cells 
contain unique guanylyl cyclase receptors, 
which allow them to respond to specific hor- 
monal signals with an increased production of 
the messenger molecule cGMP. The cells then 
change their behavior. For example, one receptor 
may control smooth muscle relaxation and be 
principally involved in the regulation of blood 
pressure, another may be involved in neural 
functions, and yet another may regulate epithe- 
lial cell secretion. These results also suggest that 
drugs specific to different forms of the guanylyl 
cyclase receptors may prove clinically relevant. 
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