The goal of this project is to study the distribution of the calcitonin gene~related peptide~immunoreactive (CGRP~IR) nerve fibers and cells in the intact rat gastric mucosa and around an experimental stress ulcer. The CGRP~IR nerve fibers branching pattern suggests the existence of columnar units of innervation that orient perpendicular to the lumen. These units may form the skeleton of a complex vasoregulatory system based on the axon reflex mechanism mediated by neuropeptides. We found a number of CGRP~producing cells (likely neutrophil leukocytes) located mainly in the lower region of the lamina propria. Our observations suggest that the effectivity of the gastric mucosal defense mechanism against chemical provocations can be improved by the involvement of leukocytes committed to produce a variety of mediator compounds. The distribution of leukocytes and their close relationship with peptidergic peripheral nerve fibers suggest that CGRP may play a role in the homing and chemotaxis of circulating immune cells. CGRP can be considered as a trophic factor regulating the gastric microcirculation, which is crucial for the maintenance and regeneration of the protective mucosal barrier. Our data confirm the hypothesis that the peripheral nervous system may collaborate with the mobile elements of the immune system associated with various organs and tissues.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002847-02
Application #
3782431
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Manglik, Aashish; Kobilka, Brian (2014) The role of protein dynamics in GPCR function: insights from the ?2AR and rhodopsin. Curr Opin Cell Biol 27:136-43