P. Hildebrand et al., PANCREATIC ACINI POSSESS ENDOTHELIN RECEPTORS WHOSE INTERNALIZATION IS REGULATED BY PLC-ACTIVATING AGENTS, The American journal of physiology, 264(5), 1993, pp. 984-993
Endothelin-1 (ET-1) and ET-3 mRNA have been found in the pancreas. We
investigated the ability of ET-1, ET-2, and ET-3 to interact with and
alter dispersed rat pancreatic acinar cell function. Radiolabeled ETs
bound in a time- and temperature-dependent fashion, which was specific
and saturable. Analysis demonstrated two classes of receptors, one cl
ass (ET(A) receptor) had a high affinity for ET-1 but a low affinity f
or ET-3, and the other class (ET(B) receptor) had equally high affinit
ies for ET-1 and ET-3. No specific receptor for ET-2 was identified. P
ancreatic secretagogues that activate phospholipase C (PLC) inhibited
binding of I-125-labeled ET-1 (I-125-ET-1) or I-125-ET-3, whereas agen
ts that act through adenosine 3',5'-cyclic monophosphate (cAMP) did no
t. A23187 had no effect on I-125-ET-1 or I-125-ET-3 binding, whereas t
he phorbol ester 12-O-tetradecanoylphorbol 13-acetate reduced binding.
The effect of cholecystokinin octapeptide (CCK-8) was mediated throug
h its own receptor. Stripping of surface bound ligand studies demonstr
ated that both I-125-labeled ET-1 and I-125-labeled ET-3 were rapidly
internalized. CCK-8 decreased the internalization but did not change t
he amount of surface bound ligand. Endothelins neither stimulate nor a
lter changes in enzyme secretion, intracellular calcium, cAMP, or [H-3
]inositol trisphosphate (IP3). This study demonstrates the presence of
ET(A) and ET(B) receptors on rat pancreatic acini; occupation of both
receptors resulted in rapid internalization, which is regulated by PL
C-activating secretagogues. Occupation of either ET receptor did not a
lter intracellular calcium, cAMP, IP3, or stimulate amylase release.