The rectal gland of the spiny dogfish shark, Squalus acanthias, secret
es chloride by a furosemide sensitive process that has been termed ''s
econdary active.'' Chloride enters the cell across the basolateral cel
l membrane via the sodium:potassium:2 chloride cotransporter. The ener
gy for this electroneutral uptake step is provided by the electrochemi
cal gradient for sodium directed into the cell. This is maintained by
Na-K-ATPase present in the basolateral cell membrane. Present as wall
in the basolateral cell membrane is a potassium conductance that permi
ts potassium to exit passively. Chloride leaves the cell across the lu
minal membrane via a chloride conductance closely similar to CFTR. The
rectal gland is thus a model for the mechanism of secondary active ch
loride transport utilized by various epithelial organs throughout the
vertebrate kingdom. This report reviews the humoral agents that regula
te the secretion of chloride by the rectal gland and the intracellular
mechanisms that mediate it. CNP, released from the heart in response
to a volume stimulus, causes the release of VIP from nerves within the
gland and together with VIP directly activates the rectal gland cell.