Chemical Messengers - University of Minnesota Duluth

• Extracellular chemical messengers bring about ... – Activating second‐messenger systems ... •The nervous system transmits electrical impulses to...

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DIRECT INTERCELLULAR COMMUNICATION Small molecules and ions

(a) Gap junctions

(b) Transient direct linkup of cells’ surface markers

INDIRECT INTERCELLULAR COMMUNICATION VIA EXTRACELLULAR CHEMICAL MESSENGERS Secreting cell

Local target cell

Paracrine

(c) Paracrine secretion

Local target cell Electrical signal

Secreting cell (neuron) Neurotransmitter (d) Neurotransmitter secretion

Blood Secreting cell (endocrine cell)

Neurohormone Blood Electrical signal

Hormone Distant target cell Nontarget cell (no receptors) (e) Hormonal secretion

Secreting cell (neuron) Nontarget cell (no receptors)

Distant target cell

(f) Neurohormone secretion Fig. 4-18, p. 92

Chemical Messengers • Four types of chemical messengers 1. Paracrines • Local chemical messengers • Exert effect only on neighboring cells in  immediate environment of secretion site

2. Neurotransmitters • Short‐range chemical messengers • Diffuse across narrow space to act locally on  adjoining target cell (another neuron, a muscle,  or a gland) 

Chemical Messengers 3. Hormones • Long‐range messengers • Secreted into blood by endocrine glands in  response to appropriate signal • Exert effect on target cells some distance away  from release site

4. Neurohormones • Hormones released into blood by neurosecretory neurons • Distributed through blood to distant target cells 

Chemical Messengers • Extracellular chemical messengers bring about  cell responses primarily by signal transduction – Process by which incoming signals are conveyed to  target cell’s interior

• Binding of extracellular messenger (first  messenger) to matching receptor brings about  desired intracellular response by either – Opening or closing channels – Activating second‐messenger systems • Activated by first messenger • Relays message to intracellular proteins that carry out  dictated response

Second Messengers • cAMP (cyclic AMP) • Ca++ • Others – Tyrosine kinase – JAK Kinase – G proteins

• All activate multiple enzyme pathways that produce  intracellular specific intracellular effects: – Secrete, contract, synthesize – All enzymes remain “on” until modulated to “off” by some controlling  process • Results in multiple intracellular “effector reactions” • Intracellular cascades

Hormones • Endocrinology – Study of homeostatic activities accomplished by  hormones

• Two distinct groups of hormones based on their  solubility properties – Hydrophilic hormones • Highly water soluble  • Low lipid solubility

– Lipophilic hormones • High lipid solubility • Poorly soluble in water

Table 4-3, p. 95

Fig. 4-19, p. 95

Testosterone, a masculinizing hormone

Estradiol, a feminizing hormone

Fig. 4-19, p. 95

Hormones • Hormones generally produce their effect by  altering intracellular proteins • Hydrophilic hormones alter preexisting  proteins via second‐messenger systems – cyclic adenosine monophosphate (cAMP) – Ca2+

• By stimulating genes, lipophilic hormones  promote synthesis of new proteins

Extracellular (first) messenger (Activates) G protein intermediary

ECF Plasma Plasma membrane membrane

Adenylyl cyclase (effector protein) G-protein (Activates) coupled receptor Second messenger 1 Binding of 2 Adenylyl extracellular cyclase converts Messenger ATP to cAMP to receptor 3 cAMP activates Activates a protein kinase A. G protein, the α subunit of which Inactive Active shuttles to protein and activates protein kinase A kinase A adenylyl cyclase. 4 Protein kinase A phosphorylates inactive designated protein, activating it. Inactive designated protein

Key Phosphate

(changes shape and function)

5 Active designated protein brings about desired response.

ICF

Active designated protein

Cellular response

Fig. 4-20, p. 97

Blood vessel Plasma protein carrier Steroid hormone

ECF

Plasma Plasma membrane membrane Cytoplasm

Cellular response

1 Free lipophilic hormone

9 New protein brings about desired response.

diffuses though plasma membrane

Steroid hormone receptor

New protein

Portion that binds hormone

8 New protein is released from ribosome and processed into final folded form.

Portion that binds to DNA

2 Hormone binds with intracellular receptor specific for it.

7 Ribosomes “read” mRNA to synthesize new proteins.

DNA-binding site (active)

6 New mRNA leaves nucleus.

3 Hormone receptor complex binds with DNA’s hormone response element. mRNA

4 Binding activates gene.

5 Activated gene transcribes mRNA.

DNA

Nucleus

Hormone Gene response element

Fig. 4-21, p. 100

Comparison of the Nervous and Endocrine Systems • The nervous system transmits electrical impulses to  skeletal muscles and the exocrine glands. • It is “wired”, sending electrical signals through distinct,  highly organized pathways.  These pathways have  interconnected parts. • The endocrine system secretes hormones (chemical  messengers) into the circulating blood to distant sites  in the body. • These glands are not connected.  They are scattered  throughout the body • Each neuron has a close anatomic relationship to its  target cells.  It has a narrow range of influence.

Comparison of the Nervous and Endocrine Systems • A neuron releases a specific neurotransmitter to a  specific target cell • The target cells have specific receptors that bind to  the neurotransmitter secreted by a neuron.   • Although that neuron can potentially signal other cells,  it is limited to the target cells in close proximity to that  neuron • A group of endocrine cells secretes a specific hormone  into the blood.  Although the hormone is circulated  throughout the body,  only specific target cells have  receptors for a specific hormone.

Comparison of the Nervous and Endocrine Systems • A hormone cannot influence all body cells.  It influences  the target cells with receptor cells that bind to that  hormone. • The nervous system coordinates rapid,  precise  responses • Its signal is an action potential.  The duration of this  signal is brief • The target cells are skeletal muscles and glands • The endocrine system controls activities of longer  duration  • This system requires a flow of blood to send a message   • The effect of a hormone lasts longer

Comparison of the Nervous and Endocrine Systems • The nervous and endocrine systems are interconnected  functionally. • Often they influence the same body process, such as the  rate of heartbeat. • Neuroendocrinology is the study of the relationships  between these two systems

Table 4-4, p. 101