239PST receptor could belong to the G protein coupled receptors family (Sanchez-
Margalet and Santos-Alvarez 1997 ).
Therefore, our group performed a two-step purification method to obtain an 80
KDa monomeric glycoprotein, partially sensitive to PT and associated with Gαq/11,
to demonstrate the G coupled protein and glycoprotein nature of the receptor;
although a final identification and complete sequencing have to be carry out, possi-
bly solved by a microsequencing technique (Sanchez-Margalet et al. 2003 , Santos-
Alvarez and Sanchez-Margalet 2000 ).
4.1 G-Proteins Coupled to Pancreastatin Receptors
G protein-coupled receptors play a crucial role in signal transduction of vertebrate
organisms. They belong to the most extensive family of receptors with more than
800 different GPCRs known so far. The structure of all of them has a common seven
membrane-spanning domains. Their mechanism of action is also common. Signal
starts with the ligand binding to the extracellular region that causes a conforma-
tional change in the seven-transmembrane domains, which is transmitted to the
third loop and the C-terminal domain, activating the associated G-protein. This het-
erotrimeric G-protein is composed of three different subunits: α, β, and γ, which can
offer a large number of permutations between them. In addition, many different
ligands are associated with diverse classes of α subunits to mediate the activation of
different signaling pathways. For example, Gαq/11 can activate IP3 signaling pathway
through phospholipase C beta, while αi1, 2 causes the inhibition of cAMP levels
(Culhane et al. 2015 ; Tuteja 2009 ).
As explained above, PST seems to bind a G-protein coupled receptor, but there is not
a direct evidence for this yet, only some indirect binding and photolabelling studies
combining with pertussis toxin and some with antibodies which block different alpha
subunits. We suppose that PST is mainly coupled to a G-protein of the Gαq/11 family, and
secondly with the Gαi1, 2 family. The specific G-protein coupled to putative PST recep-
tor has been assessed in rat liver membranes, having the Gαq protein a better functional
coupling than Gα 11 protein (Santos-Alvarez and Sanchez- Margalet 1999 , 2000 ; Santos-
Alvarez et al. 1998 ). Furthermore, it has been found, only in heart cells, a different
member of the alpha q/11 family (Gα 16 ) that is coupled to the PST receptor.
4.2 Crosstalk of Pancreastatin Receptor with Insulin Receptor
Signaling
The cross-talk between PST and insulin signaling has been largely studied in adipo-
cyte and hepatoma cells. So, it was shown that PST can impair the insulin- stimulated
auto-phosphorylation of the beta subunit of insulin receptor, in a dose-dependent
manner, (Sun et al. 1991 ). Moreover, PST was also found to interfere other steps in
Action and Mechanisms of Action of the Chromogranin A Derived Peptide Pancreastatin