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, li- 
gand-binding region. Although this receptor also 
will bind ANP, high concentrations of the pep- 
tide appear required for enzyme activation, 
which suggests the existence of a more potent 
natural peptide. 
We also have recently 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 ANP 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. 
These results suggest that drugs specific to dif- 
ferent forms of guanylyl cyclase may result in spe- 
cific physiological effects. For example, one re- 
ceptor 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. 
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