Interactive Mechanisms among Pituitary Adenylate Cyclase-Activating Peptide, Vasoactive Intestinal Peptide, and Parathyroid Hormone Receptors in Guinea Pig Cecal Circular Smooth Muscle Cells
Vasoactive intestinal peptide (VIP) causes relaxation of smooth muscle cells via both VIP-specific receptor coupled to nitric oxide synthase and VIP-preferring receptor coupled to adenylate cyclase. Because the mechanism of interaction among VIP, pituitary adenylate cyclase-activating peptide (PACAP...
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Published in | Endocrinology (Philadelphia) Vol. 139; no. 6; pp. 2869 - 2878 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Endocrine Society
01.06.1998
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Online Access | Get full text |
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Summary: | Vasoactive intestinal peptide (VIP) causes relaxation of smooth muscle
cells via both VIP-specific receptor coupled to nitric oxide synthase
and VIP-preferring receptor coupled to adenylate cyclase. Because the
mechanism of interaction among VIP, pituitary adenylate
cyclase-activating peptide (PACAP), and PTH is still unclear, the
characteristics of the receptors for PACAP and PTH in circular muscle
cells obtained from the guinea pig cecum were investigated. The effects
of an inhibitor of cAMP-dependent protein kinase [cyclic adenosine
3′,5′-monophosphorothioate (Rp-cAMPS)], guanylate cyclase inhibitors,
antagonists of these peptides, and the selective receptor protection on
the relaxing effect produced by PACAP, VIP, and PTH were examined.
PACAP-induced relaxation was significantly inhibited by a VIP
antagonist, a PTH antagonist, Rp-cAMPS, and an inhibitor of particulate
guanylate cyclase. VIP-induced relaxation was significantly inhibited
by a PACAP antagonist and a PTH antagonist. PTH-induced relaxation was
significantly inhibited by a VIP-specific receptor antagonist and
Rp-cAMPS, but not by a PACAP antagonist. A PTH antagonist significantly
inhibited a VIP-preferring receptor agonist-induced relaxation. The
muscle cells in which cholecystokinin octapeptide and PTH receptors
were protected completely abolished the inhibitory responses to VIP and
PACAP. The muscle cells in which cholecystokinin octapeptide and VIP or
PACAP receptors were protected completely abolished the inhibitory
response to PTH. This study shows that PACAP induces relaxation of
these muscle cells via both VIP-preferring receptor coupled to
adenylate cyclase and PACAP-specific receptor, and that PTH induces
relaxation of the muscle cells via PTH-specific receptor coupled to
adenylate cyclase. In addition, the results of a selective receptor
protection show that PTH does not bind to VIP receptors, and that VIP
does not bind to PTH receptor. Therefore, this study first demonstrates
the presence of one-way inhibitory mechanisms from the PTH-specific
receptor to the VIP-preferring receptor, and from the VIP-specific
receptor to the PTH-specific receptor in the mechanisms of interaction
between VIP and PTH. |
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ISSN: | 0013-7227 1945-7170 |
DOI: | 10.1210/endo.139.6.6040 |