Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endocrine tumors of the gastroenteropancreatic (GEP) axis elaborate excessive amounts of peptides that are potent intestinal secretagogues. The actions of these peptides on intestinal transport of water and electrolytes lead to the accumulation of fluid in the intestinal lumen and diarrhea. One of the most clinically relevant secretagogues is vasoactive intestinal polypeptide (VIP). Other relevant secretagogues elaborated from tumors are serotonin, prostaglandins, and kinins. Sandostatin (octreotide, Sandoz, Basle, Switzerland), a long-acting octapeptide analog of somatostatin, inhibits experimentally induced intestinal secretion and has been used successfully to treat patients with secretory diarrhea refractory to other pharmacotherapy. The effective dose is in the range of 50 to 200 micrograms, given subcutaneously two or three times daily. The mechanism for the inhibitory effect on secretion is not clearly understood but it appears to involve inhibition of the adenylate cyclase-cyclic adenosine monophosphate system as well as interference with calcium as an intercellular mediator of enterocyte secretion. A particularly interesting use of this drug has been to treat the watery diarrhea seen in patients with acquired immunodeficiency syndrome. It is also effective in other types of secretory diarrhea not associated with endocrine tumors. These include diabetic diarrhea, idiopathic secretory diarrhea of infancy, and high output ileostomy diarrhea.
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PMID:Treatment of endocrine and nonendocrine secretory diarrheal states with Sandostatin. 220 86

The potential use of somatostatin-14 and its long lasting analogue Sandostatin as antiulcer agents led us to study the functional properties of these peptides on the histamine H2-receptor H2R adenylate cyclase system in gastric glands isolated from the rat fundus. The action of the two peptides has also been compared on membrane receptors sensitive to isoproterenol and the truncated glucagon-like peptide TGLP-1. The data indicate that somatostatins inhibit selectively H2R and TGLP-1 receptor activity with similar potencies and kinetics, suggesting that the two peptides share the same receptor pool coupled with the Gi subunits of adenylate cyclase. Somatostatin-14 and Sandostatin have no evident action on the beta 2-type adrenergic receptor beta 2R. Therefore, the higher potency of Sandostatin compared to somatostatin-14 in inhibiting acid secretion is probably related to an increased stability of the analogue in vivo.
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PMID:Differential regulation of membrane receptors sensitive to histamine (H2-type), isoproterenol (beta 2-type) and glucagon-like peptides by the somatostatin analogue Sandostatin in rat gastric glands. 256 37