X-Message-Number: 11725
Date: Mon, 10 May 1999 19:50:51 -0400
From: Jan Coetzee <>
Subject: neuroprotective factor

Perspectives on pituitary adenylate cyclase activating
polypeptide (PACAP) in the neuroendocrine, endocrine,
and nervous systems.

Arimura A

Department of Medicine, Tulane University School of Medicine, New
Orleans, LA, USA.

PACAP is a pleiotropic neuropeptide that belongs to the
secretin/glucagon/VIP family. PACAP
functions as a hypothalamic hormone, neurotransmitter, neuromodulator,
vasodilator, and
neurotrophic factor. Its structure has been remarkably conserved during
evolution. The PACAP
receptor is G protein-coupled with seven transmembrane domains and also
belongs to the VIP
receptor family. PACAP, but not VIP, binds to PAC1-R, whereas PACAP and
VIP bind to
VPAC1-R and VPAC2-R with a similar affinity. Despite the sizable
homology of the structures
of PACAP and VIP and their receptors, the distribution of these peptides
and receptors is quite
different. At least eight subtypes of PACAP specific, or PAC1-R, result
from alternate splicing.
Each subtype is coupled with specific signaling pathways, and its
expression is tissue or cell
specific. Although PACAP fulfills most requirements for a physiological
hypothalamic
hypophysiotropic hormone, it does not consistently stimulate secretion
of the adenohypophysial
hormones, except for stimulation of IL-6 release from the FS cells of
the pituitary. The major
regulatory role of PACAP in pituitary cells appears to be the regulation
of gene expression of
pituitary hormones and/or regulatory proteins that control growth and
differentiation of the
pituitary glandular cells. These effects appear to be exhibited directly
and indirectly through a
paracrine or autocrine action. Although PACAP stimulates the release of
AVP, the physiological
role of neurohypophysial PACAP remains unknown. One important action of
PACAP in the
endocrine system is its role as a potent secretagogue for adrenaline
from the adrenal medulla
through activation of TH. PACAP also stimulates the release of insulin
and increases [Ca2+]i
from pancreatic beta-cells at an extremely small concentration. The
stage-specific expression of
PACAP in testicular germ cells during spermatogenesis suggests its
regulatory role in the
maturation of germ cells. In the ovary, PACAP is transiently expressed
in the granulosa cells of
the preovulatory follicles and appears to be involved in the LH-induced
cellular events in the
ovary, including prevention of follicular apoptosis. In the central
nervous system, PACAP acts
as a neurotransmitter or neuromodulator, which has been supported by IHC
and
electrophysiological methods. More important, PACAP is a neurotrophic
factor that may play an
important role during the development of the brain. In the adult brain,
PACAP appears to
function as a neuroprotective factor that attenuates the neuronal damage
resulting from various
insults.

Jpn J Physiol 1998 Oct;48(5):301-31

Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=11725