chemical communication hormones & neurotransmitters

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CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

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Page 1: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

CHEMICAL COMMUNICATION

HORMONES & NEUROTRANSMITTERS

Page 2: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Introduction

• There are three principal types of molecules used for communications– Receptors:Receptors: proteins embedded in the surface

membranes of cells– Chemical messengers:Chemical messengers: chemicals that interact

with receptors; also called ligands– Secondary messengers:Secondary messengers: chemicals that carry a

message from a receptor to the inside of a cell and amplify the message

Page 3: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

A large percent of drugs used in human medicine influence chemical communication (see Table 23.1)

- antagonist:- antagonist: a molecule that blocks a natural receptor and prevents its stimulation- agonist:- agonist: a molecule that competes with a natural messenger for a receptor site; it binds to the receptor site and elicits the same response as the natural messenger- a drug may decrease (by controlling its release) or increase (by inhibiting its removal from receptors) the effective concentration of messenger

Page 4: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Other terms and definitionsneuron:neuron: a nerve cellneurotransmitterneurotransmitter: a compound involved in communication between neurons or between a neuron and a target tissue; it acts across a synapsehormone:hormone: a compound that is synthesized in one location, travels large distances, usually in the blood, and then acts at a remote location (see Table 23.2).

The distinction between a neurotransmitter and a hormone is physiological, not chemical; it depends on whether the molecule acts over a short distance (across a synapse) or over a long distance (from the secretory organ, through the blood, to its site of action)

Page 5: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Fig. 23.1, p.573

Neuron and synapse

Page 6: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS
Page 7: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

• There are five classes of chemical messengers: • cholinergic messengers • amino acid messengers• adrenergic messengers• peptidergic messengers• steroid messengers

• Messengers are also classified by how they work; they may– activate enzymes– affect the synthesis of enzymes– affect the permeability of membranes– act directly or through a secondary messenger

Page 8: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

CLASSES OF CHEMICAL MESSENGERS

Cholinergic - acetylcholine – neurotransmitter, transfers nerve impulse to muscle cells

Amino acid – simple amino acids & modified amino acids – neurotransmitters

Adrenergic - monoamines similar to epenephrine (adrenalin) - neurotransmitters & hormones

Peptidergic – peptides & proteins – neurotransmitters & hormones

Steroid - steroids - hormones & neurotransmitters

Page 9: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS
Page 10: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

ACETYLCHOLINE

Page 11: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Acetylcholine• The main cholinergic messenger is acetylcholine

• Cholinergic receptors– there are two kinds of receptors for acetylcholine

– we look at the one that exists in motor end plates of skeletal muscles or in sympathetic ganglia

CH3-C-O-CH2-CH2-N-CH3

CH3

CH3

O

Acetylcholine (ACh)

+

Page 12: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Acetylcholine – synthesized in presynaptic cell, stored in vesicles. Release is triggered by the buildup of Ca2+ ions.

Acetylcholine moves across the synapse & forms a complex with receptor. Opens a channel for ion flow & creates a flow of charge by exchanging Na+ and K+ - this constitutes a nerve impulse.

Acetylcholine is broken down & removed from the receptor by acetylcholinesterase.

Page 13: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

• Storage and release of acetylcholine (ACh)

– the message is initiated by calcium ions, Ca2+

– the nerve cells that bring messages contain ACh stored in vesicles

– when Ca2+ concentration becomes more that about 10-4 M, the vesicles that contain ACh fuse with the presynaptic membrane of nerve cells and empty ACh into the synapse

– ACh travels across the synapse and is absorbed on specific receptor sites

Page 14: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Chem Connect 23A, p.578

Page 15: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

• Action of the acetylcholine (cont’d)

– the presence of ACh on the postsynaptic receptor triggers a conformation change in the receptor protein

– this change opens an ion channel and allows ions to cross membranes freely

– Na+ ions have higher concentration outside the neuron and pass into it

– K+ ions have higher concentration inside the neuron and leave it

– this change of Na+ and K+ ion concentrations is translated into a nerve signal

– after a few milliseconds, the ion channel closes

Page 16: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Acetylcholine

Page 17: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Acetylcholine• Removal of ACh

– ACh is removed from the receptor site by hydrolysis catalyzed by the enzyme acetylcholinesterase

this rapid removal allows nerves to transmit more than 100 signals per second

CH3-C-O-CH2-CH2-N-CH3

CH3

CH3

OH2O

CH3-C-O-O

HO-CH2-CH2-N-CH3

CH3

CH3

Acetylcholine (ACh)

+ +

Acetylcholin-esterase

+ +

Acetate Choline

Page 18: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

• Control of neurotransmission

– acetylcholinesterase is inhibited irreversibly by the phosphonates in nerve gases and some pesticides (ChemCom 23B)

– it is also inhibited by these two compounds

CH3NCH2CH2OCCH2CH2COCH2CH2NCH3

CH3

CH3 O O

CH3

CH3

CH3NCH2(CH2)8CH2NCH3

CH3

CH3

CH3

CH3Br-Br-

+ +

++

Succinylcholine

Decamethonium bromide

Page 19: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

• Control of transmission (cont’d)

– another control is to modulate the action of the ACh receptor– because ACh enables ion channels to open and propagate

signals, the channels themselves are called ligand-gated ion ligand-gated ion channelschannels

– the attachment of the ligand to the receptor is critical to signaling

– nicotine in low doses is a stimulant; it is an agonist because it prolongs the receptor’s biochemical response

– nicotine in high doses is an antagonist and blocks the action of the receptor

Page 20: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Amino Acids• Amino acid messengers

– some amino acids are excitatory excitatory neurotransmittersneurotransmitters; examples are Glu, Asp, and Cys

– others are inhibitory neurotransmittersinhibitory neurotransmitters; examples are Gly and these three

H3NCH2CH2SO3- H3NCH2CH2COO- H3NCH2CH2CH2COO-

Taurine -Alanine -Aminobutyric acid(GABA)

+ + +

Page 21: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Amino Acid Messengers• Receptors

– Glu has at least five subclasses of receptors– the best known among these is the N-methyl-D-aspartate

(NMDA) receptor

– this receptor is a ligand-gated ion channel– when Glu binds to the receptor, the ion channel opens, Na+ and

Ca2+ ions flow in, and K+ ions flow out NMDA is an agonist and also stimulates the receptor

-OOC-CH2-CH-COO-

NH2+

CH3

N-Methyl-D-aspartate

Page 22: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Adrenergic Messengers

• Monoamine messengers

HO

N

NH3+

H

HO

HONH3

+

N

N

H

H

NH3+

Epinephrine

Serotonin Dopamine Histamine

+

+

Norepinephrine

HO

HO

NOH

HO

HO

NH3+

OHCH3

H

H

Page 23: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

G protein hydrolyzes GTP,activating adenylate cyclase which forms cAMP

cAMP activates protein kinase; ATP phosphorylates catalytic unit

Catalytic unit phosphorylates ion-translocating protein, & opens ion gates.

Page 24: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Adrenergic Messengers

• When norepinephrine is absorbed onto the receptor site– the active G-protein hydrolyzes GTP– the energy of hydrolysis activates adenylate

cyclase

Page 25: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Cyclic AMP (cAMP)– cAMP is synthesized in cells from ATP

N

NN

N

NH2

O

OHO

HHH

CH2

H

O

POO-

Cyclic-adenosinemonophosphate

(cAMP)

N

NN

N

NH2

O

OHOH

HHH

CH2

H

OPO-

O-O O P O P

O

O- O-

O

Adenosine triphosphate(ATP)

adenylatecyclase

+ PO-

O-O O P O-

O

O-

Pyrophosphate

Page 26: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Adrenergic Messengers

– cyclic AMP activates protein kinase by dissociating the regulatory (R) unit from the catalytic (C) unit

Page 27: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Adrenergic Messengers

– the catalytic unit phosphorylates the ion-translocating protein that blocks the channel ion flow

– the phosphorylated ion-translocating protein changes its shape and position and opens the ion gate

Page 28: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Adrenergic Messengers

• Removal of the signal– when the neurotransmitter or hormone

dissociates from the receptor, adenylate cyclase stops the synthesis of cAMP

– the cAMP already produced is destroyed by the enzyme phosphodiesterase, which catalyzes the hydrolysis of one of the phosphodiester bonds to give AMP

Page 29: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Adrenergic Messengers• Control of neurotransmission

– the G-protein-adenylate cyclase cascade in transduction signaling is not limited to monoamine messengers

– among the other neurotransmitters and peptide hormones using this signaling pathway are glucagon, vasopressin, luteinizing hormone, enkephalins, and P-protein

– a number of enzymes can be phosphorylated by protein kinases and the phosphorylation controls whether these enzymes are active or inactive

Page 30: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Adrenergic Messengers• Removal of neurotransmitter

– the body inactivates monoamines by oxidation to an aldehyde, catalyzed by monoamine oxidases (MAOs)

HO

HO

NH3+

OH

MAO

HO

HO

NOH

CH3

H

H

MAO

HO

HO

HOH

Epinephrine

+

Norepinephrine

O

Page 31: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

• Histamine– H1 receptors are found in the respiratory tract where

they affect the vascular, muscular, and secretory changes associated with hay fever and asthma; antihistamines that block H1 receptors relieve these symptoms

– H2 receptors are found mainly in the stomach and affect the secretion of HCl; cimetidine and ranitidine block H2 receptors and thus reduce acid secretion

N

N

H

H

NH3+

COO-

H+ N

N

H

H

NH3+ CO2

Histamine

+

+

+ histidinedecarboxylase+

L-Histidine

Page 32: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

• The first brain peptides isolated were the enkephalins– these pentapeptides are present in certain nerve cell terminals– they bind to specific pain receptors and seem to control pain

perception

• Neuropeptide Y, a potent orexic, affects the hypothalamus• Substance P, an 11-amino acid peptide is involved in the

transmission of pain signalsTyr-Gly-Gly-Phe-LeuLeucine enkephalin

Tyr-Gly-Gly-Phe-MetMethionine enkephalin

Page 33: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS
Page 34: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Peptidergic Messengers• All peptidergic messengers, hormones, and

neurotransmitters act through secondary messengers– glucagon, luteinizing hormone, antidiuretic

hormone, angiotensin, enkephalin, and substance P use the G-protein-adenylate cyclase cascade. Others such as vasopressin use membrane-derived phosphatidylinositol (PI) derivatives

-O-P-O

OHOHOH

OH

OHH

H H

H

H

H

O

O-Inositol 1-phosphate

Page 35: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Steroid Messengers

• A large number of hormones are steroids– these hormones are hydrophobic and, therefore, cross

plasma membranes by diffusion– steroid hormones interact inside cells with protein

receptors– most of these receptors are located in the nucleus, but

small numbers also exist in the cytoplasm– once inside the nucleus, the steroid-receptor complex

can either bind directly to DNA or combine with a transcription factor

Page 36: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS
Page 37: CHEMICAL COMMUNICATION HORMONES & NEUROTRANSMITTERS

Modes of hormone action

Activate enzymes ex. – epinephrine

Alter gene transcription & the synthesis of enzymes ex. – steroids

Alter the permeability of membranes ex. - insulin