Endocrinology, lecture on the Relationship between Peptides in the GI tract and Brain
XXVIII. Guts and Brains
A. Gastrointestinal Neurons
1. enteric nervous system (part of the autonomic)
a. innervates muscle, blood vessels, mucosa and interneurons
i. muscle: substance P, VIP, enkephalin
ii. vessels: NPY + NE
iii. mucosa: VIP, somatostatin, substance P, NE
iv. interneurons: somatostatin, 5-HT, VIP
2. endocrine cells are scattered in the epithelial lining
of gastric glands, intestinal crypts, and villi
3. neural and endocrine secretions diffuse into blood
a. release from axon terminals increases local effect
i. each nerve type has specific patterns of projection
(1) projection may be neuroendocrine:
neurohemal organ
4. colocalization
a. neurons with peptides and classical transmitters
i. with ACh: substance P, CCK, somatostatin, GRP, NPY
ii. with NE: NPY, somatostatin
b. peptides may be colocalized
i. VIP + dynorphin,
ii. NPY + somatostatin, NPY + CCK
5. stimulation of enteric secretion of neuropeptides
a. vagal, mechanical, or chemical
B. Neural Regulators of GI endocrine function
1. parasympathetic ACh stimulates gastrin and PP
a. ACh inhibits somatostatin
2. sympathetic NE/Epi inhibit gastrin, PP, somatostatin + VIP
when binding to a receptors
3. GRP/bombesin also stimulates gastrin
4. Hypocretins (HCrt) stimulate autonomic function + GI hormones
C. Distribution of Neuropeptides in the Gastrointestinal system
1. stomach: VIP, somatostatin, GRP/bombesin, ghrelin
metenkephalin, 5-HT, b-endorphin
2. small intestine: CCK, VIP, somatostatin, neurotensin (NT),
substance P, metenkephalin, 5-HT, b-endorphin
3. pancreas: TRH, CCK, substance P, GRP/bombesin, PP
4. large intestine: VIP, somatostatin, NT, substance P, 5-HT
D. Brain distribution
1. CCK, VIP, somatostatin, neurotensin, substance P, 5-HT, grehlin,
HCrt, metenkephalin, b-End, TRH, GRP/bombesin, neuromedin B,
2. found in the hypothalamus, hippocampus, amygdala,
substantia nigra (except CCK), and cortex
3. stimulate/inhibit: appetite, GI secretion and motility, glucose regulation,
thermoregulation, cardiovascular function, locomotor activity,
nociception, neuroendocrine secretion
E. Regulation of appetite and food intake
1. Hypothalamus regulates feeding and satiety
a. Lateral (LH) = feeding center
i. MCH (melanin-concentrating hormone) elevates feeding
ii. orexins = hypocretins produced in LH
(1) HCrt1 (OrxA), HCrt2 (OrxB)
iii. orexins stimulate appetite & feeding
(1) Hcrt/Orxs also stimulate: gastric secretion,
metabolic rate, GI hormone release
(2) stimulate arousal, wakefulness
b. Ventromedial(VMH) = satiety center
i. OrxA/HCrt1 increases food intake
by delaying the onset of a behaviourally normal satiety
c. also involved ARC, PVN, DMN
i. Ghrelin is made in ARC
(1) stimulates feeding
(2) Ghrelin also made by the stomach epithelium
ii. NPY in PVN stimulates excessive eating
(1) AgRP (agouti related peptide) is colocalized
with NPY leads to obesity
(2) inhibited/regulated by 5-HT2A activity
d. food intake is also stimulated by stimulated by:
i. anandamide binding CB1 receptors
(1) endogenous cannabinoid
(2) may be influenced by
endorphins and enkephalins
ii. galanin triggers craving for fatty foods
e.appetite/feeding inhibited by: CCK, leptin, CRF, POMC, CART,
VIP, somatostatin, PP, PYY, oxytomodulin, GLP1 (glucagon-like peptide)
neurotensin, TRH, GRP/bombesin
F. Brain-Gut Axis
1. neurons of the CNS and enteric NS interact
a. via afferent and efferent pathways
to influence digestive processes
2. GI hormones provide feedback
a. regulate satiety and thermoregulation
3. \ digestive function is integrated
via responsiveness to central and preipheral secretion of the
same peptides