Endocrinology, lecture on the Relationship between Peptides in the GI tract and Brain
USD Department of Biology
Endocrine Glands
2nd Messengers
Nuclear Receptors
Genetic Regulation
Hormone Synthesis
Receptor Regulation
Hypothalamo-Hypophysial Communication
Tropic Hormones
Neurohypophysial Nonapeptides
Thyroid Axis
Adrenal Axis
Adrenal Medulla
Osmotic-Pressure Balance
Reproductive Endocrinology
Somatic Axis
Growth Factors
Immune Factors
Ca++, PO4 Homeostasis
Pancreatic Hormones
Feeding and GI Hormones
Guts 'n Brains
Brain Hormones
Endocrine Evolution
Figures for Endocrionology
text:Vertebrate Endocrinology5th Edition - David O. Norris:
Read pages 427-485 for this lecture
acronyms    end
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. Orexins/Hypocretins (Orx/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, 
		   Orx/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

XXIX. Hormones made in the Brain