Nervous and Neuroendocrine regulation of the pathophysiology of cholestasis and of biliary carcinogenesis

Table 1 Neuroendocrine hormones affecting cholangiocyte biology

Hormone	Receptor	Effect on cholangiocyte biology	Reference
Secretin	SR	Stimulates HCO3- secretion through the increase of cAMP/PKA and opening of CFTR	1, 34-43
Somatostatin	SSTR2	Counteracts the effect of secretin; stimulates bile absorption	44, 45
Insulin	IR	Counteracts the effect of secretin	46
ET-1	ETA-ETB	Counteracts the effect of secretin; reduces the SR expression	47
VIP	unspecified	Increases HCO3- and water secretion	48, 49
Bombesin	unspecified	Increases HCO3- and water secretion	50
Gastrin	CCK-B/gastrin	Counteracts the effect of secretin; reduces cell proliferation	40, 51
Estrogens	ERα-ERβ	Stimulate cell proliferation	52-55
Serotonin	5HT1A-5HT1B	Synthesized and secreted by cholangiocytes in the course of cholestasis. Counteracts the effect of secretin and reduces cell growth	58
GH/IGF-1	GH-R-IGF-1R	Stimulate cell proliferation	59