Effect of dopamine on amylase secretion from guinea pig pancreatic acinar cells in vitro.

Summary Dopamine has been shown to effect pancreatic flow, prote in output and amylase secretion in a variety of species. However, there is conflicting evidence regarding the role of dopamine on amylase release in vitro. Specific studies were conducted to evaluate the effect of dopamine and to compare its effects with other substances on basal- and secretagogue-stimulated amylase secretion in a guinea pig dispersed pancreatic acinar cells preparation. Dopamine (10 −6 M) induced a small, but significant (P −6 M) including bombesin, cholecystokinin-octapeptide (CCK-8) and carbachol as anticipated induced significantly larger responses. Other substances tested (10 −6 M) including thyrotropin-releasing hormone (TRH) and muscimol were without effect. Complete dose-response studies (10 −11 −10 −3 M) in the presence of bombesin, CCK-8 and carbachol revealed that dopamine does not affect amylase release in response to these secretagogues. These findings suggest that dopamine is a weak stimulant of amylase secretion in vitro, and that it may therefore play a minor role in regulation of pancreatic enzyme secretion. Several factors including vascular, hormonal and neural have been implicated in regulation of pancreatic exocrine secretion (1). In particular, autonomic nervous system activity, notably cholinergic, has been shown to affect the secretory status of the pancreatic acinar cell (2–6). In addition, several biologically active peptides including bombesin, cholecystokinin (CCK), secretin, vasoactive intestinal peptide (VIP), substance P, gastrin and stimulation of cholinergic (muscarinic) receptors with carbachol have been shown to stimulate pancreatic enzyme secretion both in vivo and in vitro (1). Certain controversy regarding the role of the sympathetic nervous system in regulation of pancreatic exocrine secretion does exist. For example, several studies with agonists and antagonists of noradrenergic and dopaminergic receptor subtypes suggest a stimulatory effect on pancreatic fluid, electrolyte and enzyme secretion (7–9). However, these responses are species-specific and variations inherent to the model have been described (11–12). Dopamine administration has been shown to stimulate pancreaticbicarbonate and enzyme secretion in a variety of species including mice (10) dogs (8, 13, 14) and man (15). Radioligand binding studies with 3 H-dopamine have revealed the presence of high-and low-affinity dopamine binding sites in dog pancreatic acinarcells (16). Stimulation of these receptors has been correlated with dose-dependent increases in intracellular cAMP levels (16). These biochemical observations suggest that activation of D 1 (linked to adenylate cyclase) dopamine receptors induces a pancreatic exocrine secretory response. This is not entirely unexpected since other substances including VIP, secretin and cholera toxin have been shown to stimulate pancreatic enzyme secretion through a cAMP-dependent mechanism (16). This study was designed to determine the effect of dopamine on basal-and secretagogue (i.e. bombesin, CCK-8 and carbachol)-stimulated amylase release in an in vitro dispersed pancreatic acinar cell preparation.