Summers

Neurobiology text: Principles of Neural Science - Kandel, Schwartz and Jessell: Read pages 239-240, 262, 295 for this lecture end acronyms end

XXVII.  Transmitters without Vesicles:

   Gases & Purinergic transmitters   			back to XXVI. 2nd Messenger Systems


	A. Nitric Oxide (NO) formed from Arginine


		1. catalysed by NO synthase (NOS) ® 1 amino (NH2 - guanidino group)
		   removed from Arg



				     /® NO
			a. Arg -----® L-citrulline (Cit)


			b. NOS activated by Ca++/Calmodulin


				i. Ca++ influx via NMDA (N-methyl-D-aspartate) receptor


	B. \ Glu stimulates NO production 


		1. ACh  muscarinic receptors also increase Ca++ influx
		   via PLC and thereby ­ NO


			a. other systems increase Ca++ influx and
			   ­ NO


				i. H1, 5-HT2


	C. No vesicles - small gas molecule diffuses across synapse


		1. very short lived: half life = 3-5s


		2. synthesized on demand


		3. may be colocalized with vesicle bound transmitters such as VIP


	D. No receptor - NO binds to Fe in the heme of GC (guanylyl cyclase)


		1. conformational change activates enzyme (i.e. GC)


		2. increased cGMP


			a. phosphorylation of PK (protein kinase)


				i. PK activates an enzyme or other protein


	E. NO + O2 ® NO2 or NO3


		1. NO may also travel (and carry regulatory information) from post-
		   to presynaptic cells


			a. = retrograde messenger


			b. functions this way in LTP (long-term potentiation) in hippocampus
			   and other areas


				i. enhanced synaptic transmission


					(1) ­ post-synaptic current
					
					
						(a)­ neuronal population activity


					(2) LTP is not confined by activity of cells or synapses
					
					
						(a) spreads to any synapse within 70 mm
						
						
						(b) NO spreads in all directions
						
						
						(c) LTP may be caused by many neuronal molecules


					(3) may last from hours to weeks


				ii. neuronal plasticity


					(1) increases dendritic spines in hippocampus and VMH


						(a) synaptogenesis


	F. Meets the requirements, if unconventionally, for neurotransmitter


	G. Found in all basket and granule cells of the cerebellum; and 1-2% of
	   cerebral cortex, hippocampus and corpus striatum


		1. 2% have widely diffused projections to other parts of the brain


		2. mediates learning - a type of plasticity - via LTP


			a. but it's toxic at high levels over a long period


				i. may be causative factor in cell death in Alzheimer's
				   and Huntington's diseases


				ii. it is a mechanism of  immune cells (e.g. macrophage)
				    killing foreign organisms


		3. found in neurons which innervate blood vessels,
		   gastrointestinal tract, and penis


			a. the neurotransmitter responsible for stimulating erection


			b. mediates ACh stimulation of peristalsis and gut relaxation


			c. also mediates the action of other transmitters in vasodilation


	H. Other gaseous transmitters: CO


		1. synthesized in neurons by heme oxygenase


			a. HO activated by reduction from cytochrome P450 reductase


				i. CP450R has a similar amino acid sequence to NOS


		2. CO also increases cGMP levels


		3. found in olfactory neurons


		4. transmitter associated with regulation of hyperthermia
		
		
	I. Purinergic transmitters
	
	
		1. ATP & Adenosine
		
		
			a. reciprocal synthetic/catabolic relationship
			
			
			b. not "classic" neurotransmitters - ATP found in vesicles
			   Adosine is not
			
				i. neither stored nor released classically

				
		2. released by neurons and glia
		
			a. acts presynaptically - facilitating or inhibiting
			   transmitter release
			   
			b. act postsynaptically and nonsynaptically
		
		
		3. ATP receptors = P2t,2u,2x,2y,2z
		
		
			a. biphasic response - early excitatory
			
			
				i. breakdown to Adenosine
				
				ii. 2o inhibitory effect
			
			
			b. P2t,2u,2y - G
						
			c. P2x,2z - ionotropic
			
		
		4. Adenosine receptors = A1,2a,2b,3
		
		
			a. A1 - highly expressed in brain

				i.  Gi & Gp

			b. A2 & 3 mostly non-neural

				i. A2 - Gs & Gp

				ii. A3 - Gp
		
		

XXVIII. Autonomic Function: ACh and NE

Top