Stimulus–secretion coupling in exocrine pancreas: possible role of calmodulin

Abstract

Many calcium-mediated effects in mammalian cells may be activated by calcium-calmodulin stimulated enzymes. These effects are inhibited by various antidepressant drugs which bind to and inactivate calmodulin. In the current study, calmodulin was identified by affinity chromatography and gel electrophoresis in the cytoplasm of dispersed rat pancreatic acinar cells. Its role in enzyme secretion was assessed by evaluating the effects of various antidepressants drugs on the enzyme secretory process. Chlorpromazine, trifluoperazine, thioridazine, chlorprothixene and amitriptyline inhibited amylase secretion stimulated by carbachol, A-23187, and cholecystokinin-pancreozymin but not that elicited by dibutyryl cyclic AMP secretin or vasoactive intestinal peptide (VIP). Haloperidol, sulpiride, phenobarbital, and ethanol were without effect on secretagogue-stimulated enzyme release. Only those agents which blocked secretion also inhibited 45Ca release stimulated by carbachol from isotope preloaded cells. The data suggest that calmodulin may have a functional role in pancreatic enzyme secretion.

Stimulation of amylase and sialic acid releases from dog submandibular gland slices by pilocarpine or high K+ medium: A possible role of calmodulin for their releases.

“…MERRITT et al (1981) reported that phenothiazine derivatives, trifluoperazine and prochlorperazine, dose-dependently inhibited the secretion of prolactin by thyrotropin-releasing hormone or 35 mM K+ in the anterior pituitary gland. YAGA et al (1981) andHEISLER et al (1981) also reported that chlorpromazine, trifluoperazine, and W-7 markedly inhibited the release of amylase, insulin, and glucagon stimulated by carbachol and glucose in rat pancreas. In addition, KANAMORI et al (1981) and ASANO et al (1982) showed that W-7 and prenylamine dose-dependently blocked the contraction of rabbit aortic strips induced by norepinephrine, serotonin, histamine, or high K+ concentrations.…”

Purification and characterization of myosin light-chain kinase from the rat pancreas

“…Higher concentrations of CCK-8, which cause submaximal stimulation and profound alterations in acinar-cell morphology [43], were associated with even greater light-chain labelling [5]. Moreover, observations that agents which are capable of blocking light-chain phosphorylation inhibit pancreatic secretion are consistent with a role for regulated myosin phosphorylation in secretion [14].…”

“…The enzyme, myosin light-chain kinase (MLCK), is characterized by absolute dependence on Ca2" and calmodulin, and a narrow substrate specificity for a light-chain subunit of myosin. Inhibition of enzyme release from the pancreas by a calmodulin antagonist suggests that a MLCK may participate in exocrine pancreatic secretion [14].…”

Participation of Ca2+ and calmodulin in rat pancreatic enzyme secretion induced by secretin, forskolin, and dibutyryl cyclic AMP.

“…Furthermore, Cat + binds with regulatory protein such as CaM and regulates a multitude of intracellular enzyme systems which influence secretory processes (KAKIUCHI and YAMAZAKI, 1970;CHEUNG, 1980;MEANS and DEDMAN, 1980). CaM antagonists such as neuroleptic drugs (LEVIN and WEISS,1977;WoNG and CHEUNG, 1979;HEISLER et al, 1980) may not be suitable for use in cell biology because they are highly toxic to intact cells and are more soluble in the hydrophilic than in the aqueous phase (SEEMAN et al, 1974). In the present study we used W-7 (HIDAKA et al, 1978) which entered cells more readily and bound to CaM with greater affinity than neuroleptic drugs.…”