Animal Phys molecules

Gap junction proteins (connexins)

direct signalling proteins

• direct exchange of ions and small messengers (cAMP, ATP, GTP)

insulin

secreted by B-cells

binds to RTK (receptor tyrosine kinase) → stimulates GLUT4

glucagon

secreted by a-cells of pancreas

binds to GPCR in liver → activates adenylate cyclase → cAMP → PKA → glycogenolysis

oxytocin

hormone from posterior pituitary

binds to GPCR to stimulate uterine contraction

arginine vasopressin (AVP)

peptide hormone from posterior pituitary

regulates water retention and vasoconstriction via GPCR

atrial natriuretic peptide (ANP)

peptide hormone from heart

lowers bp by binding receptor guanylate cyclase → increases cGMP → activates PKG → vasodilation

cortisol

hormone from adrenal cortex

increases blood glucose under stress via HPA axis, binds intracellular receptors to regulate gene transcription

aldosterone

regulates sodium retention and electrolyte balance

estrogen / testosterone / progesterone

bind intracellular receptors to regulate gene expression and reproductive traits

ecdysone

steroid hormone in insects that controls molting

epinephrine

catecholamine

from adrenal medula

binds adrenergic GPCRs to raise heart rate and blood glucose

norepinephrine

catecholamine

sympathetic neurotransmitter with similar roles to epinephrine

dopamine

catecholamine

acts via GPCR (D1, D2 receptors) involved in reward, motor control

serotonin (5-HT)

monoamine

acts via GPCR (5-HT1, 5-HT2) or ionotropic 5-HT3 receptor; modulates mood, gut function

histamine

amine

inflammation, gastric acid secretion, wakefuleness

Thyroid hormones (T3/T4)

amine but hydrophobic

cross membranes and regulate gene transcription

acetylcholine (ACh)

classical neurotransmitter

binds nicotinic receptors (ionotropic, excitatory) or muscarinic receptors (metabotropic)

prostaglandins / leukotrienes

lipid-derived eicosaniods

local paracrine signalling, inflammation and pain

anandamide

endocannabinoid lipid messenger

ATP / AMP / Adenosine

purine messengers 

act via P2X (ionotropic) or P2Y (metabotropic) receptors

Nitric Oxide

activates guanylate cyclase → cGMP → vasodilation

Intracellular receptors

ligand diffuse through membrane → receptor-ligand complex binds DNA → changes gene transcription

ligand gated ion channels (ionotropic)

Activate heterotrimic G-proteins → regulate ion channels or enzyme activity → second messenger

receptor tyrosine kinases (RTKs)

ligand binding induces dimerization and autophosphorylation → recruits SH2-domain proteins (GRB2, src) → activates Ras-MAPK pathway → cell growth, metabolism

Receptor guanylate cyclase

converts GTP → cGMP → activates PKG → smooth muscle relaxation

G protein subunits

activate or inhibit amplifier enzymes (adenylate cyclase, phospholipase C, phosphodiesterase)

adenylate cyclase

converts ATP→cAMP; activates by G_s, central to many hormone and neurotransmitter pathways

cAMP

second messenger that activates protein kinase A (PKA)

PKA

phosphorylates metabolic enzymes, ion channels, mediates effects of glucagon, epinephrine

Phospholipase C (PLC)

activated by G_q: cleaves PIP2 → IP3 + DAG

IP3

second messenger; releases Ca2+ from ER

DAG

second messenger; activates PKC

PKC (protein kinase C)

phosphorylates proteins to relax smooth muscle

Ras (small GTPase)

activated by RTKs via GRB2/SOS; triggers MAPK cascade

MAP kinase pathway

Ras → Raf (MAPKKK) → MEK (MAPKK) → ERK (MAPK); controls proliferation, differentiation

SNARE proteins (synaptotagmin, syntaxin, SNAP-25, synaptobrevin)

mediate synaptic vesicle fusion for neurotransmitter release; synaptotagmin senses Ca2+

Voltage-gated ion channels

generate and propagate action potentials; Ca2+ entry at synapse triggers vesicle fusion

GLUT2

pancreatic B-cells, liver

senses and transports glucose bidirectionally

GLUT4

muscle, adipose

translocates to membrane in response to insulin

Glutamate receptors

AMPA/NMDA receptors → depolarization (EPSP)

GABA

GABA_A receptors → hyperpolarization (IPSP)

CHH (crustacean hyperglycemic hormone)

receptor guanylate cyclase → increased cGMP → mobilizes glucose

nicotinic acetylcholine recepetor

found at neuromuscular joints

ACh binds → channel opens → Na+ influx → muscle depolarization → contraction

AMPA receptor

ligand = glutamate

permeable to Na+ and K+; mediates fast excitatory transmission in CNS

NMDA receptor

requires both glutamate and depolarization

allows Ca2+ entry → triggers synaptic plasticity (eg LTP in learning/memory)

kainate receptor

subtype of glutamate receptor

contributes to excitatory postsynaptic currents in certain brain regions

GABA_A receptor

ligand = GABA

Cl- channel; opening because hyperpolarization → inhibitory postsynaptic potential (IPSP)

glycine receptor

ligand = glycine

Also a Cl- channel; inhibitory in spinal cord

5-HT3 receptor

ligand: serotonin

cation channel mediating rapid excitatory transmission in CNS and gut

P2X receptor

ligand = ATP

nonselective cation channel; involved in pain perception and inflammation

B-adrenergic receptor

ligand=epinephrine/norepinephrine

Coupled G_s → activates adenylate cyclase → increases cAMP → activates PKA → heart rate increases → glycogen breakdown increases

a1-Adrenergic receptor

ligand: epinephrine / norepinephrine 

coupled to G_q → activates PLC → IP3 + DAG → increase Ca2+, smooth muscle contraction (vasoconstriction)

a2-adrenergic receptor

ligand = epinephrine

coupled to G_i → inhibits adenylate cyclase → lowers cAMP; presynaptic autoreceptor decreasing further NE release

Muscarinic ACh receptors

• M1, M3, M5 couple to G_q → PLC → IP3/DAG → smooth muscle contraction, gland secretion

• M2, M4 couple to G_i → decreases cAMP, open K+ channels → slows heart rate

Metabotropic Glutamate Receptors (mGluRs)

Group I (mGluR1/5) couple to G_q → PLC pathway → excitatory

Groups II and III (mGluR2/3/4/6/7/8) couple to G_i → inhibit cAMP → generally inhibitory

GABA_B receptor

ligand = GABA

Coupled to G_i → inhibits adenylate cyclase, opens K+ channels → slow inhibitory effect

5-HT1 receptors=

ligand=seratonin

Couples to Gi → lowers cAP → inhibitory (eg in migraine therapy)

5-HT2

ligand=seratonin

Couples to G1 → PLC → increased Ca2+ → excitatory

P2Y receptors

ligand = ATP, ADP

usually Gq or Gi coupled → regulate platelet aggregation, vascular tone

Trk receptors

ligands = neurotrophine (eg BDNF)

RTKs involved in neuronal growth, survival, synaptic plasticity via Ras-MAPK and PI3K pathways

Atrial Natriuretic Peptide (ANP) receptor

a receptor guanylate cyclase

ligand binding → directly converts GTP to cGMP → activates PKG → vasodilation → natriuresis

Growth factor receptors (EGFR, etc)

ligands = EGF, PDGF

RTKs, stimulate cell division via Ras-MAPK cascade

CLOCK / BMAL1

transcriptional activators (start cycle)

form heterodimer during the day and activate Per, Cry, and Rev genes

Per

during day Per genes are transcribed + accumulate in cytoplasm

forms Per/Cry complex at night and inhibits CLOCK/BMAL1 activity → this stops further transcription of Per and Cry (negative feedback)

Cry

during day Cry genes are transcribed + accumulate in cytoplasm

forms per/cry complex at night and blocks CLOCK/BMAL1 → inhibits its own transcriptional activity (negative feedback)

Rev-erba

activated by CLOCK/BMAL1 during the day

transcriptional repressor of Bmal1 → fine tunes rhythm by making sure Bmal1 levels drop when its not needed → helps reset the cycle

SCN (suprachiasmatic nucleus)

body’s master circadian clock

receives light info from eyes and sends timing signals to other hypothalamic regions and pineal gland

pineal gland

produces melatonin after receiving signal from SCN

melatonin

hormone that communicates nighttime information to tissues

promotes sleep onset (higher at night)

PVH (paraventricular nucleus of hypothalamus)

regulate HPA axis and corticosteroid release

ensures daily cortisol rhythm → links circadian rhythm to stress hormone production