Melatonin and Eicosanoids

Sleep and wakefulness

Melatonin has a major role in regulation of ________ and ______________.

Pineal gland; 3rd

Melatonin is produced by the _________ gland, located behind the ____rd ventricle.

Tryptophan; serotonin

Melatonin is synthesized from _______________ with ____________ as an intermediate.

Blue light; supra-chiasmatic nucleus

_______ light suppresses melatonin. Photic information from retina transmitted to hypothalamus and SNS via the ______-____________ nucleus, then to pineal gland.

Light; darkness

Secretion of melatonin is regulated and inhibited by __________, but stimulated by _____________.

Norepinephrine; beta-adrenergic

Melatonin is stimulated by darkness by retinal photoreceptors releasing ________________, which activated _______-adrenergic receptors in the pineal gland.

Serotonin

The activation of beta-adrenergic receptors in pineal gland cause ______________ to be converted to melatonin.

Hyperpolarized; Blind

Melatonin is inhibited by light by retinal photoreceptor cells becoming ________________, which inhibits release of norepinephrine. _________ can still have light-induced suppression of melatonin as long as light is coming through their retina.

Supra-chiasmatic nucleus

Circadian rhythm of melatonin secretion is controlled by an endogenous pacemaker in the _______-______________ nucleus.

Lighting; modify; suppress

Environmental ___________ alters timing of circadian rhythm. Day-night cycles can ___________ rhythm. Brief pulses of light ____________ melatonin.

2-4 AM

Secretion of melatonin usually begins at dusk and peaks at ___-___ AM.

Time zones; night-shift

Shifts in melatonin secretion after flights across ______ zones and in ________-shift workers.

1-3 years old; declines

Melatonin increases until __-__ years old in humans, then it _____________.

MT1 and MT2

Melatonin activates ______ and ______ receptors, which are G-protein coupled receptors.

Reproduction

Melatonin regulates/affects sleep, circadian rhythm, mood, sexual maturation and ________________, and aging.

Anti-inflammatory

Melatonin may have ______-______________ effects on immune system. Results in immunocompetent cells with a high affinity for melatonin receptors.

Cancer; enhances

May have beneficial effects on __________, since removing pineal gland ____________ tumor growth.

Damage; free radicals

Melatonin affects aging by decreasing cell ____________ due to free ____________.

Speed; duration/quality

Melatonin affects _________ of falling asleep and _____________/__________ of sleep.

Mood; depression

Abnormal circadian rhythms implicated in _______ disorders. Can cause ____________ and seasonal affective disorder.

Bright-light

___________-_________ therapy can decrease depression and help SAD.

Reproductive; increases

Hours of darkness/season linked to _______________ activity. Melatonin _______________ during long winter nights.

GnRH; estrous

When melatonin decreases, ________ starts to increase, causing more __________ cycles.

Puberty; pituitary-gonodal axis

Decreases in melatonin at ____________. Melatonin decrease activates the pituitary-____________ axis.

Ovarian; progesterone

Melatonin may affect sex steroid hormone synthesis and modulate ___________ function. Melatonin receptors on ovaries stimulate progesterone synthesis.

Alopecia X; decrease

Melatonin is used to treat __________ ___ in dogs because it may _____________ GnRH, which decreases LH/FSH effects on adrenal androgen precursors.

Anxiety and seizure activity

Melatonin decreases ____________ and ____________ activity.

Sedation and incoordination

Short-term side effects of melatonin are minimal and include ____________ and __________________.

Eicosanoids

What is the group of signaling molecules synthesized by oxidation of 20-carbon essential fatty acids (EFA)?

Inflammatory

When consuming EFAs in diet, they affect _____________ pathways.

Arachidonic acid and Eicosapentaenoic acid

What are the 2 precursors of Eicosanoids?

Actions

Balance between each type of eicosanoids (omega-3 and omega-6) determines actions.

Less inflammatory

Omega-3 EFAs yield eicosapentaenoic acid, which is ______ inflammatory.

Pro-inflammatory

Omega-6 EFAs yield arachidonic acid, which is ______-inflammatory.

PG

Eicosanoids have a 2 letter abbreviation = _____

PGE

Eicosanoids have one A-B-C letter = ______

PGE2

Eicosanoids have a subscript indicating number of double bonds = _______

5; 3; 5

Omega-3 FAs yield eicosapentaenoic acid (has ___ double bonds) and contains prostanoids with ___ double bonds and leukotrienes with ___ double bonds.

4; 2; 4

Omega-6 FAs yield arachidonic acid (has ___ double bonds) and contains prostanoids with ___ double bonds and leukotrienes with ___ double bonds

Cyclopentane ring

Prostaglandins A-I differ in substituents on the ______________ ring.

a,B-unsaturated ketones

PGAs are a,B-________________ ketones.

B-hydroxyl ketones

PGEs are B-____________ ketones.

1,3-diols

PGFs are 1,3-_______.

Lessen; arachidonic acid

Major function of EPA cascade is to ____________ inflammatory effects of ______________ acid prostanoids.

Prostaglandins (PG), prostacyclins (PGI), thromboxanes (TX)

What are the 3 prostanoids in the AA cascade?

Leukotrienes (LT) and Lipoxins (LX)

AA cascade also contains what other 2 substances?

Stimulate; inhibit

Overall effects of AA cascade are to ____________ inflammatory responses, modulate pain and fever, reproductive functions, __________ gastric acid secretion, blood pressure regulation, and platelet activation/inhibition.

Cats; delta 6-desaturase

________ can't convert linoleic acid to arachidonic acid due to low _________ __-_____________ enzyme.

Omega-3; prostanoids

Eicosapentaenoic acid (EPA) cascade is formed from ___________-___ EFAs and form mostly _______________.

Phospholipase A

What releases arachidonic acid from phospholipids in cell membrane?

COX1 and COX2

Arachidonic acid will be oxygenated by cyclooxygenase (_________ and _________) to make prostanoids.

Omega-6

Arachidonic acid (AA) cascade is formed from ____________-____ FAs.

5LOX

Arachidonic acid will be oxygenated by lipooxygenase (________) to make leukotrienes.

Short; inflammation

Major actions of prostanoids derived from arachidonic acid: Local hormones with autocrine or paracrine action, ________ half-life (seconds to minutes), mediated by specific receptors, mediate _________________ (except for lipoxins).

PGE2

What prostanoid derived from arachidonic acid controls smooth muscle contraction, brochoconstriction, pain, heat, and fever?

PGI2

What prostanoid derived from arachidonic acid controls vasodilation and inhibits platelet aggregation?

Linoleic acid (18 C EFA) and Gamma linolenic acid

What are the 2 dietary precursors of arachidonic acid?

TXA2

What prostanoid derived from arachidonic acid controls vasoconstriction and stimulates platelet aggregation?

Inhibit; decrease

Non-steroidal anti-inflammatory drugs (NSAIDs) ___________ prostanoid formation, and therefore ___________ inflammation, redness, swelling, pain, and heat.

Firocoxib (Previcox), deracoxib (Deramaxx), meloxicam (Metacam), piroxicam (Faldene), celecoxib (Celebrex)

What 5 NSAIDs inhibit only COX2 and have less side effects?

Aspirin, carprofen (Rimadyl), flunixin (Banamine), phenylbutazone, ibuprofen, naproxen

What 6 NSAIDs inhibit COX1 and COX2?