Somatostatin and its analogue
octreotide have been used for two decades to treat oesophageal variceal haemorrhage. The
drug was introduced because of its capacity to decrease portal venous pressure without major side effects. In clinical trials assessing the efficacy of
somatostatin and long-acting analogues in arresting variceal haemorrhage, conflicting results have been obtained. Furthermore, in haemodynamic studies evaluating the effects of
somatostatin and analogues in patients with
cirrhosis, divergent effects were observed. The main reason for these differences is probably related to different affinities of the drugs for different
somatostatin receptor subtypes. The effects of
somatostatin and analogues are mediated via five different
G-protein coupled receptors (
somatostatin receptor subtypes 1-5), which regulate the activity of
ion channels (Ca2+, K+, Na+ and Cl-) and
enzymes (
adenyl cyclase,
phospholipase C,
phospholipase A2,
phosphoinositide 3-kinase and
guanylate cyclase) responsible for the synthesis or degradation of intracellular second messengers including
cyclic AMP,
inositol 1,4,5-trisphosphate,
diacylglycerol and
cyclic GMP. Despite universal use of
somatostatin, the cellular and biochemical mechanisms of its effects in
portal hypertension are relatively poorly studied and remain incompletely understood. In this review, we summarize relevant signal transduction of
somatostatin and analogues, the haemodynamic effects of the drugs and the possible mechanisms by which these effects are mediated.