2332.1 Effects on Glandular Secretions
2.1.1 Endocrine Secretion
PST Inhibits Glucose Stimulated Insulin Secretion in Endocrine Pancreas
Since its isolation (Tatemoto et al. 1986 ) PST has been designated as an inhibitor of
glucose stimulated insulin secretion, especially the first phase (Tatemoto et al.
1986 ). This effect was achieved both in vivo, in porcine pancreas, as well as in vitro,
in beta cell lines. Thus, the cell line RIN m5F, a model of Langerhans islet beta
cells, under PST treatment, showed significantly inhibition of insulin secretion
stimulated by glyceraldehyde, carbachol, or ionophore A23187 (Hertelendy et al.
1996 ). Moreover, the inhibition of insulin secretion by PST seems to keep close
relationship with elevation of cytosolic Ca2+ levels (Sanchez-Margalet et al. 1992 ).
Even more, PST didn’t inhibit insulin secretion stimulated by mastoparan and phor-
bol myristate acetate ester (PMA), being those mechanisms not dependent on Ca2+.
In general, all inhibitory effects of pancreastatin have been shown to be pertussis
toxin sensitive, suggesting that PST could perform its action through a G-protein
regulated Ca2+-dependent mechanism, a common feature of other physiological
inhibitors of insulin secretion (Hertelendy et al. 1996 ). Insulin release seems to be
affected by PST in the presence of multiple physiological stimuli, such as glucose,
arginine (Efendic et al. 1987 ), hormones GIP, VIP, CCK-8 (Peiro et al. 1989 ) or
glucagon (Efendic et al. 1987 ), and some drugs like 3-isobutyl-1-methylxanthine or
sulphonylurea (Schmidt and Creutzfeldt 1991 ). However in rat perfused pancreas,
PST did not affect the somatostatin and glucagon release (both insulin mediated
processes), while in canine pancreas and pig (Ohneda et al. 1989 ) rat PST had no
effect on glucose-induced insulin release, suggesting that PST mediated effects
could be species dependent.
PST Restricts Parathyroid Hormone Secretion
PST also exerts inhibitory effects on thyroid-parathyroid axis, being the
calcitonin- producing C cells which take care of the active PST production, since
the parathyroid gland, despite of being an important producer of CGA, doesn’t
yield PST (Cohn et al. 1982 ). So, PST produced by C-cells inhibits secretion of
parathyroid hormone (PTH) in porcine, bovine and cultured parathyroid cells
under low calcium condition or phorbol ester stimulation (Fasciotto et al. 1989 ;
Drees and Hamilton 1992 ), while, enhanced PTH secretion in parathyroid cells
has been observed when PST peptide was blocked with specific antibodies
(Fasciotto et al. 1990 ). Moreover, PST also inhibited the transcription of the PTH
and CGA genes and decreased the stability of the respective mRNAs (Zhang
et al. 1994 ). Since the parathyroid cells don’t produce PST, it seems to be unlikely
any autocrine regulation of PTH, while paracrine/endocrine regulation via C
cells should not be excluded.
Action and Mechanisms of Action of the Chromogranin A Derived Peptide Pancreastatin