Neurohumoral transmission

Introduction in Neurons and the transmission of impulses in nervous system

1. Neurohumoral Transmission Mizbaah Kaunain 1 st year M.Pharm Pharmacology

2. GENERAL CONSIDERATIONS

3. PERIPHERAL NERVOUS SYSTEM : The autonomic nervous system (ANS ): controls the so-called visceral functions of the body The   somatic nervous system(SNS): is associated with the voluntary control of body movements via skeletal muscles.  Four types of nerve fibers are found in most nerves:      somatic afferent (sensory)  and  efferent (motor) fibers  visceral afferent (sensory)  and  efferent (motor)  fibers     

4. The visceral afferent and visceral efferent fibers form the ANS and the somatic afferent and somatic efferent fibers form the SNS

5. In ANS- nerve impulses are transmitted from the CNS to peripheral ganglia via pre ganglionic neuron and then to effector cells via post ganglionic neuron. Thus, an impulse from the CNS must travel on the fibers of  two  neurons to reach an effector cell controlled by that system(exception is the  adrenal medulla )  In SNS- an impulse can travel from the CNS to a given effector cell on the fibers of a  single  neuron .

6. Sympathetic and Parasympathetic NS T he sympathetic and parasympathetic divisions of the ANS can be regarded as  physiological antagonists ,   Most organs are innervated by both sympathetic and parasympathetic fibers Sympathetic Parasympathetic Control the body's response during perceived threat. Control the body's response while at rest. Very short neurons, faster system Longer pathways, slower system Increases contraction, heart rate Decreases  heart rate neurons are mostly adrenergic: epinephrine / norepinephrine neurons are cholinergic: acetylcholine Called as Thoracolumnar Called as craniosacral

7. A neuron can receive chemical messages at various active sites called receptors , three groups of which are considered important : • Soma-dendritic receptors : located on the cell body and dendrites. Related to generation of action potential or protein synthesis. • Presynaptic receptors: Located in or near the axon terminals, when activated, primarily modify the function of the terminal region. These receptors are of two types : ( 1) Auto receptors : Auto receptors respond to the neuron’s own transmitter, and are involved in synaptic feed back mechanism. They are usually inhibitory to further release of the transmitter (2 ) Heteroreceptors . somatic motor fibres of the cholinergic system have excitatory presynaptic receptors. e.g . angiotensin II type 2 (AT2) receptors on adrenergic cells . • Postsynaptic receptors : a re associated with the target organs/tissues

8. NEUROHUMORAL TRANSMISSION T ransmission across synapses and neuroeffector (or neuromuscular) junctions is mediated by chemical substances called  neurohumoral transmitters  or more simply  neurotransmitters .  The transfer of nerve impulses from presynaptic to post synaptic neuron by means of a humoral agent e.g. Biogenic amine , an amino acid or a peptide is neurohumoral transmission

9. CRITERIA FOR TRANSMITTERS It should be present in the presynaptic neurone in nerve endings (usually along with enzymes synthesizing it). It should be released in the medium following nerve stimulation and its presence must be demonstrable and detectable in extracellular fluids Its application should produce responses identical to those produced by nerve stimulation. Its effects should be antagonized or potentiated by other substances which similarly alter effects of nerve stimulation and also have a system of inactivation

10. NEUROTRANSMITTERS Acetylcholine: Involved in Learning ,memory and muscle movement Adrenaline Noradrenaline Dopamine :Imparts arousal ,mood states, thought process and physical movements 5-Hydroxytryptamine(5-HT) GABA: Main inhibitory neurotransmitter in the nervous system Glutamate : Main excitatory neurotransmitter in the nervous system Nitric Oxide Neuropeptide Y(NPY) Opioid peptides Endocannabinoids etc.…

11. PRINCIPLES OF CHEMICAL TRANSMISSION DALE’s principle Neuromodulation Pre synaptic Post synaptic Denervation super sensitivity

12. DALE’S PRINCIPLE This rule states that a neuron performs the same chemical action at all of its synapses. But it was overturned by many examples of co-release NEUROMODULATION PRESYNAPTIC MODULATION: Presynaptic terminals that synthesize and release transmitters are often sensitive to transmitter substances and to other substances E.g. In heart Ach inhibit NA and NA inhibit Ach release. This is mutual presynaptic inhibition. POSTSYNAPTIC MODULATION: Chemical mediators act on the postsynaptic structures to alter their excitability or spontaneous firing pattern due to changes in Calcium or potassium channel function , mediated by second messengers.

13. DENERVATION SUPERSENSITIVITY If a nerve is cut and its terminals are allowed to degenerate, the structure supplied by it becomes supersensitive to transmitter substances released by the terminals Thus skeletal muscle ,which normally responds to large amounts of injected acetylcholine given directly into the arterial blood supply, will, after denervation, respond by contracture to much smaller amounts

14. CO-TRANSMISSION

15. STEPS IN NEUROTRANSMISSION The term conduction is reserved for the passage of impulse along an axon or muscle fiber The term transmission refers to passage of impulse through synaptic or neuromuscular junction. With the exception of the local anaesthetics ,very few drugs modify axonal conduction in the doses employed therapeutically.

16. AXONAL CONDUCTION

17. JUNCTIONAL TRANSMISSION The arrival of the action potential at the axonal terminals initiates the transmission of an excitatory or inhibitory impulse across neuroeffector junction The transmitter (excitatory or inhibitory) is stored in prejunctional nerve endings within ‘synaptic vesicles ’ The basic steps in neurochemical transmission involves Synthesis Storage Release Recognition and Metabolism of neurotransmitter