Endocrinology, lecture on Adrenal Medullary Catecholamines
USD Department of Biology
Endocrinology
Summers
Hormones
Endocrine Glands
Receptors
Homeostasis
2nd Messengers
Nuclear Receptors
Genetic Regulation
Hormone Synthesis
Receptor Regulation
Hypothalamo-Hypophysial Communication
Tropic Hormones
Neurohypophysial Nonapeptides
Thyroid Axis
Steroids
Adrenal Axis
Adrenal Medulla
Osmotic-Pressure Balance
Reproductive Endocrinology
Prolactin
Somatic Axis
Growth Factors
Immune Factors
Ca++, PO4 Homeostasis
Pancreatic Hormones
GI Hormones
Guts 'n Brains
Brain Hormones
Neurosteroids
Neuropeptides
Endocrine Evolution
Figures for Endocrionology
text:Vertebrate Endocrinology5th Edition - David O. Norris:
Read pages 283-287 for this lecture
acronyms    end
XVI. Chromaffin Tissue - Adrenal Medulla 		


	A. Chromaffin tissue in mammals is found in the center (medulla) of the
	   adrenal gland

		1. in other classes chromaffin tissue is associated with "cortical"
		   tissue but is not necessarily medullary 

			a. juxtaposition is related to function and is derived
			    evolutionarily many times


	B. Chromaffin tissue is highly innervated by the sympathetic nervous system


		1. may be thought of as postsynaptic neuron


			a. which terminates on capillary bed


				i. derived from neural crest tissue similar to those of
				    the sympathetic ganglia


					(1) nerve growth factor (NGF) 
					    plays an important role in development

		2. stimulated by the neurotransmitter ACh


			a. all presynaptic neurons of the sympathetic and
			   parasympathetic ns secrete ACh


			b. postsynaptic neurons of the sympathetic ns secrete NE


		3. Chromaffin tissue secretes NE (1/3),
		    but mostly Epi       (in humans/rats)


			a. catecholamines


XVII. Catecholamines


	A. DA, NE, and Epi


		1. each is secreted as an end product


			a. all are hormones


				i. DA and NE most often act as neurotransmitters


				ii. Epi is also a central neurotransmitter


	B. Biosynthesis									


		1. aa Tyrosine is converted by tyrosine hydroxylase


			a. limiting step


				i. stimulated by ACTH


				ii. activated by phosphorylation via cAMP/Protein Kinase A


					(1) negative feedback by DA, NE, Epi


		2. into DOPA (L-DOPA is the only natural form)


			a. DOPA decarboxylase = aaa decarboxylase
			                        (aaa= aromatic amino acid)

		3. DA = dopamine


			a. DBH = dopamine b-hydroxylase


				i. stimulated by ACTH


		4. NE


			a. PNMT = phenylethanolamine N-methyltransferase	


				i. stimulated by glucocorticoids


					(1) delivered by a local portal system


			b. TH, DBH, & PNMT are similar proteins with common
			   gene coding sequences


		5. Epi


	C. Catabolism


		1. very rapid, each catecholamine into different metabolites


		2. 2 main enzymes						


			a. cathechol O-methyltransferase = COMT


				i. Epi ® metanephrine or NE ® normetanephrine


			b. monoamine oxidase = MAO


				i. very common


				ii. deaminates


	D. Receptors and Uptake


		1. Adrenergic Receptors					
		

			a. a


				i. a1 binds Epi > NE


					(1) activates IP3 /DG /PKC /Ca++


					(2) smooth muscle contraction: arteries in skin, kidney
					    and digestive system, sphincters, iris (pupil dilates)


				ii. a2 binds Epi > NE


					(1) may be presynaptic or postsynaptic


						(a) presynaptic for local negative feedback


					(2) activates Gi ® inhibits AC/cAMP


					(3) may oppose actions of  b-receptors: ¯ insulin
					    secretion & lypolysis


			b. b								 	         	


				i. b1  &  b2 bind Epi > NE


					(1) activate Gs /AC /cAMP /PKA


				ii. b1  mostly cardiac


					(1)  HR, contractility, conduction
					    velocity, and coronary artery dilation


					(2)  lypolysis


				iii. b2  glycogenolysis and gluconeogenesis
				    and insulin secretion


					(1) dilate blood vessels in skeletal muscle but relax
					    smooth muscles in the digestive tract, uterus, and lungs


					(2) stimulate renin secretion


		2. Dopaminergic receptors are grouped into 2 main subfamilies D1 and D2


			a. DA1: DA1 & DA5
			   DA2: DA2, DA3, DA4


			b. 2nd messengers: 


				i. D1  subfamily = Gs  / cAMP   


				ii. D2 family = Gi


		3. Uptake, Re-uptake


			a. catecholamines are taken up by cells
			   in which they are stored or degraded


			b. neural cells which make DA or NE re-incorporate neurotransmitter
			   secreted, and reuse it


				i. active transport


			c. non-neural cells actively take up catecholamines
			   and then degrade them with COMT

XVIII. Osmotic Balance - Renin/Angiotensin