Summers

Neurobiology text: Principles of Neural Science - Kandel, Schwartz and Jessell: Read pages 282-283 for this lecture end

 XVIII. Catecholamines 			back to XVI. Neurotransmitters + ACh

	A.  Synthesis


		1. precursor:  tyrosine  (Tyr)


			a. tyrosine hydroxylase
			   (TH, an oxidase, rate limiting enzyme)


		2. L-DOPA       (levo-dihydroxyphenylalanine)


			a. DOPA decarboxylase      (aromatic aa decarboxylase)


		3. dopamine (DA)


			a. CO2  released


			b. dopamine b-hydroxylase (DBH)


				i. DA neurons have no DBH


					(1) genes encoding enzymes independently regulated


					(2) genes for TH, DBH, & PNMT very similar


					(3) on the same chromosome


					(4) regulation can be coordinated

		4. norepinephrine (NE)

			a. phenylethanolamine-N-methyltransferase (PNMT)

				i. NE neurons have no PNMT

					(1) found in the adrenal medulla

					(2) also centrally

		5. epinephrine (Epi)

		6. tyramine and octopamine may be transmitters
		    in invertebrates

	B. Reuptake and Degradation

		1. most synaptically released DA is recaptured

			a. DAT = membrane transporter
			   (facilitated [Na+] transport)

				i. similar to NE and GABA transporters

				ii. there is also a VAT (vesicular amine transporter)
				     to put loose cytoplasmic DA into vesicles 

			b. reuptake is the main way by which
			    transmitter function is terminated

			c. the rest is catabolized by monoamine oxidase (MAO),
			    catechol-O-methyltransferase (COMT), 
				aldehyde dehydrogenase, or aldehyde reductase

			d. intraneuronal catabolism produces 3-O-methyl DA

			e. synaptic catabolism produces  DOPAC
			    (3,4-dihydroxyphenylacetic acid)  

		2. most synaptic NE is recaptured (NET) &
		    \ transmitter function is terminated

			a. catabolism involves COMT, MAO,
			    aldehyde dehydrogenase and redutase

				i. sympathetic catabolism results in vanilly-mandelic acid

				ii. central catabolism results in  MHPG
				    (3-methoxy-4-hydroxyphenylglycol)

					(1) intraneuronal catabolism has DOPEG
						(3-4- dihydroxyphenylglycol) as intermediate

					(2) synaptic normetanephrine
 
		3. Epi catabolised as is NE

			a. MHPG is a common metabolite

			b. synaptic catabolism produces metanephrine

	C. Receptors

		1. DA1-5  -  in two main subgroups

			a.  DA1 stimulatory (Gs  protein stimulates cAMP)


				i. DA5 is a subtype of DA1 (Gs)

					(1) subtype means very similar: genes + structure

			b.  DA2  inhibitory (Gi blocks cAMP)

				i. DA3 is a subtype of DA2 (Gi high limbic concentrations)

				ii. DA4 is also a DA2 subtype (Gi)

		2. Adrenergic   (NE and Epi)

			a. a1 & a2 bind Epi > NE ;   b1 & b2 bind Epi > NE

				i. a1A-D in brain and blood vessels (Gp); 
				   a2A-C in presynaptic nerve terminals (Gi brain); 
				   b1 & b2 in cerebrum and cerebellum (Gs);
				   b3 in fat (Ca++ channel)

XIX. Indoleamines

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