Aside from Epinephrine, one hormones released during stess is Cortisol.

Differentiate Epinephrine from Cortisol with regards the following:

a.control of secretion, b. mechanism of action c. effect on cells

Epinephrine

Control of secretion

Integral part of fight or flight response

Epinephrine

Stimulus to sympathetic nervous system via splanchnic nerve

Stimulation of cholinergic preganglionic fibers

Acetylcholine

Nicotinic acetycholinereceptors

Epinephrine

Depolarization of chromaffin cell membrane

Increased permeablity of membrane to sodium

Influx of calcium ions through voltage-gated calcium channel

Exocytosis of secretory granules

Epinephrine (bloodstream)

Epinephrine

Epinephrine
Simple feedback loop

Sensor Hormone Target 2

Target 1

Other hormone

or metabolite exert negative feedback to down-regulate its own synthesis at the presynaptic alpha-2 adrenergic receptor

Epinephrine synthesis is under control of CRH-ACTH-Cortisol axis 1. ACTH stimulates synthesis of Dopamine and Norepinephrine 2. Cortisol upregulates PNMT in chromaffin cells

Epinephrine

Mechanism of Action

Epinephrines actions mediated through adrenergic receptors: 1, 2, 3 and 1, 2 Epinephrine does not cross cell membrane binds to cell surface receptors adrenergic receptors

1.

Binds to 1 receptors of liver cells Activates inositol-phospholipid signaling pathway Activates heterotrimeric Gq protein coupled to Phospholipase C Second messenger: Calcium and/or Phosphoinositides (IP3, DAG) Signaling phosphorylation by activation of Protein kinase C: - Glycogen synthase inactivation - Phosphorylase kinase activation Activation of glycogen phosphorylase glycogenolysis

Epinephrine
2. Binds to -adrenergic receptors of liver and muscle cells Activates cAMP signaling pathway Activates heterotrimeric Gs protein coupled to Adenylyl cyclase Second messenger: cAMP Signaling phosphorylation by activation of Protein kinase A: - Glycogen synthase inactivation - Phosphorylase kinase activation Activation of glycogen phosphorylase glycogenolysis

Epinephrine

Epinephrine

Effects on cells

Effects on metabolism Gluconeogenesis and receptors on liver cells Glycogenolysis receptors on liver and muscle cells Glucagon secretion receptors Insulin secretion on cells Lipase activity, Lipolysis plasma free fatty acids receptors on muscle and liver leading to oxidation

Epinephrine
Effects on Cardiovascular system Heart Rate 1 receptor Cardiac Contractility 1 receptor Conduction velocity 1 receptor Systolic blood pressure Cardiac output Arteriolar dilatation 2 receptor

Epinephrine
Effects on other systems muscle K+ uptake - receptors muscle relaxation - receptors - Gastroinestinal - Urinary - Bronchial Dilatation of pupils Modulate ADH release receptors stimulate -- receptors inhibit Renin release - receptors

Epinephrine
Recept Linked or Type Enzyme 1 PLC Second Messen ger IP3 and DAG cAMP cAMP cAMP Effects Binds to 1 receptors of liver cells Glycogenolysis Gluconeogenesis Platelet aggregation Dilation of pupils Cardiac contractility Heart rate Glycogenolysis Vasodilation in muscle and liver cells Muscle relaxation Gluconeogenesis Lipolysis Glycogenolysis

2 1 2

Adenyl cyclase Adenyl cyclase Adenyl cyclase Adenyl cyclase

cAMP

Cortisol

Control of Secretion

Synthesis and secretion stimulated by ACTH (Corticotrophin) Release of ACTH is stimulated by Corticotrophin-releasing hormone (CRH) CRH

G protein receptor ( G alpha-s) cAMP Active PKA Corticotrophs

Cortisol

Activated Ca+2 channels

Influx of Calcium

Corticotrophs

Exocytosis of ACTH

Melanocortin-2 receptor coupled to G protein

adrenal medulla

Adenylyl cyclase

Cortisol

cAMP active PKA

adrenal medulla

Enzymes converting cholesterol to pregnenolone synthesis of Cortisol

Subsequent release of Cortisol from zona fasculata

Secretion of cortisol exhibits diurnal variation Peaks early morning hours Dimnishes late in afternon and early evening

Cortisol

Cortisol

Mechanism of Action

Cortisol(lipid soluble) diffuses to cell membrane intracellular receptor Glucocorticocoid receptors (GR) GR (unbound form) is complexed to Heat Shock protein (HS protein) HS protein dissociates from Cortisol-GR complex Cortisol-GR complex translocate to nucleus Cortisol-GR complex associates with Glucocorticoid response elements (GRE) GRE induces or represses transcription genes Cortisol or transcription alter mRNA synthesis

Cortisol

Cortisol

Effects on cells

Effects on metabolism Gluconeogenesis glucose utilization Deamination of AA by hepatocytes glucose transport to fat cells Conversion of AA to glucose protein stores in all cells Plasma and liver proteins except liver cells Fatty acid mobilization from fat cells FFA plasma concentration Ketogenesis Fatty acid oxidation

Cortisol
Tissue/ Organ/ Organ System Muscle Bone Connective Tissue Kidneys CNS Fetus Effect of Cortisol maintains contractility and work performance of cardiac and skeletal muscle mass increases bone resorption inhibits collagen synthesis

Vascular System required for maintenance of normal blood pressure increase GFR modulates excitability, behavior and mood of individuals Facilitate maturation of fetus

Inflammation and Inhibit inflammatory and immune response Immune response

Discuss the role of epinephrine in the utilization of glucose during exercise

Role of Epinephrine in Exercise

During exercise, net effect of epinephrine shunt blood toward the active muscles while maintaining coronary and cerebral blood flow Delivery of substrate for energy production to the critical organs Increase circulating blood glucose through: Gluconeogenesis on liver cells Glycogenolysis on liver and muscle cells Glucagon secretion Insulin secretion Lipase activity, Lipolysis plasma free fatty acids on muscle and liver leading to oxidation Calorigenesis Glucose utiization

Role of Epinephrine in Exercise

Give the expected results and its physiologic basis of the experiment. Interpret the actual results and explain any discrepancy with the expected results. Give the conclusion of the experiment

Expected Results
Blood sugar level before and after 10 minutes after injection of epinephrine
Increase in blood sugar level

Blood sugar level before and after 10 minutes after injection of saline
Increase in blood sugar level

Blood sugar level first and second sample of rat C (no injection given)
No change in blood sugar level

Expected Results
Liver Glycogen of Rats A,B,C
Decrease glycogen in Rat A No change in glycogen for Rats B & C

Muscle Glycogen of Rats A, B, C

Decrease glycogen in Rat A No change in glycogen for Rats B & C

Actual Results
ANOVA 0min Between Groups Within Groups Total Between Groups Within Groups Total Between Groups Within Groups Total Sum of Squares 300.536 df 2 Mean Square 150.268 3097.384 F .049 Sig. .953 102213.687 33 102514.222 35 4020.169 91532.270 95552.439 7382.682 2 33 35 2 3691.341 .965 3823.565 .391 2010.084 .725 2773.705 .492

10min

20min

126177.660 33 133560.342 35

Mean blood sugar levels between 0, 10 min and 20 min were equal among the 3 groups.

Actual Results

T-test

Paired Samples Correlations N Pair 1 0min & 10min Pair 2 10min & 20min 12 12 Correlatio Sig. n .748 .787 .005 .002

Epinephrine Group

Paired Samples Statistics Mean N Pair 1 0min 10min Pair 2 10min 20min 97.950 12 122.117 12 122.117 12 127.767 12

Std. Deviation 51.4254 47.7836 47.7836 63.7821

Std. Error Mean 14.8452 13.7939 13.7939 18.4123

Paired Samples Test

Actual results
Sig. (2tailed) 95% Confidence Interval of the Difference t df

Paired Differences

Pair 0min 1 10min

Mean Std. Std. Lower Upper Deviatio Error n Mean 35.409310.2218 -1.6687 11 24.16 46.6646 2.364 67

.038

Pair 10min - 39.441011.3856 19.4096 -.496 11 2 20min 5.650 30.7096 0

.629

There was a significant difference between the mean blood glucose levels before and 10 minutes after epinephrine injection but none between 10 and 20 minutes after epinephrine injection.
30

Actual Results
T-test
Saline Group
Paired Samples Correlations N Correlati Sig. on Pair 1 Pair 2 0min & 10min & 10min 20min 12 12 .918 .955 .000 .000

Descriptive Statistics N 0min 12 10min 12 20min 12 Valid N 12 (listwise)

Minimum 38.0 51.0 71.0

Maximum 314.0 293.0 371.0

Mean 97.367 100.617 120.717

Std. Deviation 73.9668 63.7832 83.3079

31

Actual Results
Paired Samples Test Paired Differences Sig. (295% Confidence Interval of the tailed) Difference Lower Upper .710 .037 t df

Mean Std. Deviatio n Pair 0min - 29.5433 1 10min 3.250 0 Pair 10min - 29.3512 2 20min 20.10 00

Std. Error Mean 8.5284 8.4730

-22.0209 15.5209 -.381 11 -38.7489 -1.4511 -2.37211

There was no significant difference between the mean blood glucose levels before and 10 minutes after saline injection, however, a significant difference was noted between 10 and 20 minutes after saline injection. 32

Actual Results
T-test
Control Group
Paired Samples Correlations N Correlation Sig. Pair 1 0min & 10min 12 Pair 2 10min & 20min
Paired Samples Statistics Mean Pair 1 0min 10min Pair 2 10min 20min N Std. Deviation 34.3000 44.3796 44.3796 21.5020 Std. Error Mean 9.9015 12.8113 12.8113 6.2071
33

.826 .741

.001 .006

12

91.550 12 98.883 12 98.883 12 94.483 12

Actual Results
Paired Samples Test Paired Differences t df Sig. (295% Confidence Interval of the tailed) Difference

Mean Std. Deviatio n Pair 0min - 25.1125 1 10min 7.333 Pair 10min - 3 4.400 31.9025 2 20min 0

Std. Lower Upper Error Mean 7.2493 -23.28908.6224 11 1.012 9.2094 -15.869924.6699 .478 11

.333 .642

There was no significant difference in the mean blood glucose level before and 10 minutes later and between 10 and 20 min later in the control group.

Discrepancies
Results may be affected by the following: Subject mice might be agitated too much causing increase release of epinephrine Clerical errors e.g.: miscalculation, errors in weighing Isolated glycogen was not completely dried causing discrepancy in weighing

Conclusion

Epinephrine (Adrenaline)

Stimulates glucose production and inhibits glucose use Stimulates lipolysis and ketogenesis Inhibits secretion of insulin Stimulates glycogenolysis on liver and muscle cells shunt blood toward the active muscles while maintaining coronary and cerebral blood flow Provide energy substrates to critical organs e.g. Brain, heart.

Net effect:

plasma glucose, FFA and ketoacids Adrenaline Rush