UC Berkeley

Abstract

Stimulation of substance P release from sensory nerves by incretin hormones

By

Fahima Mayer

Doctor of Philosophy in Endocrinology

University of California, Berkeley

Professor Gregory W. Aponte, Chair

The communication between the gut and the brain is very complex and is regulated by various systems, such as the endocrine, immune, autonomic, and the enteric nervous system. Food intake has been known and thought to play a major role in this communication. Previously the laboratory of my graduate work showed that guanine nucleotide-binding protein couple receptor (GPCR) GPR93 (also known as lysophosphatidic acid 5 (LPA5) or GPR92) is located at the apical side of the gut lumen and senses nutrients in the lumen of the gut. This receptor was the first to be discovered to be localized on sensory nerves and yet respond to components in mesenteric lymph fluid (MLF) induced in response to the diet. The lymphatic fluid contains cells and molecules from the interstitial fluid (IF) that surrounds specific tissues. My study was to examine if the afferent sensory nerves that innervate the mesenteric lymphatic vasculature could be activated by diet induced molecules of the MLF to form a system of nutrient sensing of the interstitium. I observed that MLF stimulated primary cultured mouse dorsal root ganglia (DRG) sensory neurons. I discovered that Glucagon-like peptide 1 (GLP-1) or Glucose-dependent insulinotropic polypeptide (GIP) as model molecules of the MLF stimulated those neurons resulting in the release of Substance P (SP). GLP-1 and GIP are incretin hormones, which induce blood glucose levels to go down after a meal. The results of this study showed a new mode of action for GLP1 and GIP incretin hormones that is extra-pancreatic and how the peripheral tissues and the central nervous system could be stimulated by molecules of the interstitium/MLF via afferent sensory nerves.