Burger showed that volume expansion activated the secretion by the rectal gland. Volume expansion, not osmolality, appeared to be the stimulus that activated secretion. Solomon, using an explanted gland preparation, in which a gland was connected to a live fish only through its blood supply, demonstrated that a humoral agent mediated the response to volume expansion, because volume expanding the fish caused the explanted gland to secrete. But the nature of the humoral agent was not identified. Solomon then examined the possibility that the shark heart contained natriuretic peptides that could activate the rectal gland. Extracts from shark atria or ventricle activated the gland, as did serum from sharks that had been volume expanded. A natriuretic peptide from the shark heart (CNP) was identified and shown to activate the gland. But the activation process proved to be more complex than anticipated, and the natriuretic peptide released from the heart caused the release of VIP from nerves within the gland that in turn activated the gland. Shark CNP also had a direct effect on the gland, it bonded to gland membranes, has a receptor, and activated guanylate cyclase. Its ultimate cellular effect probably involves also the inositol phospholipid cascade.