ATP and adenosine + receptors Flashcards
ATP and adenosine is…
purines
How many different purinergic receptors is there in humans, and are they metabotropic or ionotropic?
Two types: P1R and P2R. P1R are metabotropic. P2X (subtype of P2R) is ionotropic and P2Y is metabotropic.
How many receptors are there of each type?
P1R: 4 (A1, A2A, A2B and A3)
P2X: 7 (1-7)
PY2: 8 (1, 2, 4, 6, 11, 12, 13, 14)
Describe the topology of the P2X Rs.
Trimers; each monomer has 2 TMs, the TM 2 regions make up the pore. The C- and N-terminus are both cytoplasmic. Big extracellular loop between TM1 and TM2 containing multiple Cys-bridges.
Name an antagonist of the A2A receptor.
Caffeine
What are the agonists of the P1 Rs and the P2 Rs?
P1 Rs are adenosine receptors, P2 Rs are ATP receptors.
What are some of the positives effects of caffeine, and what are some of the negative?
Positive: increased attention, alertness and metabolic rate. Lower risk of cardiovascular diseases and diabetes. Decreased fatique.
Negative: increased vasoconstriction and blood pressure. Reduced control of fine motor movements. Stimulation of urination. Anxiety (and addiction?).
What are some of the symptoms of caffeine overdose?
Ringing ears, seeing flashes, increased sensitivity of skin, rapid heart beat in an irregular rhytm, anxiety and headache.
Which diseases are the A2A R believed to be involved?
Parkinson´s disease and Alzheimer´s disease.
Explain how ATP is involved in pain.
Damaged cells leak ATP. ATP binds to P2X3 R on nociceptors causing a Na^+ influxdepolarizing the cell. The depolarization triggers voltage gated Na^+ channels to open resulting in an action potential traveling to the brain, where th sensation of pain is perceived.
Explain how ATP is believed to be involved in the mediation of inflammatory pain.
ATP binds to P2X4 on macrophages causing a Ca^2+ influx inducing a signal cascadde involving COX´s and resulting in the release of PGE2. PGE2 then binds to a prostglandine type E R on noceceptors, activating the G-s-alpha, which activate an adenylyl cyclase. The Adenylyl cyclase convert ATP to cAMP, which activates a PKA, that phosphorylate and activates a TRPV1. This result in Na^+ influx and an action potential traveling to the brain.
Explain how ATP is involved in chemosensory transduction.
Low PO_2/high PCO_2 in arterial blood leads to the release of ATP by carotid glomus cells. ATP binds to P2X3 R on sensory neurons near the glomus cells, inducing an action potential, that travel to the medulla oblongata via the dorsal root ganglion, resulting in increased breathing.
Explain how ATP is involved in the signaling of the bladder content.
Full bladder leaks ATP, ATP binds to P2X3 R on nerve in urothelium, causing a depolarization triggering voltage gated Na^+ channels to open resulting in an action potential. The AP travels to the spinal cord via the dorsal root ganglion, then signal is tranducted from the dorsal horn to the ventral horn and further via the spinothalamic tract to thalamus. Here the sensation of feeling the need to pee is perceived.
What are the four classical signs of inflammation and what causes them?
1) dolor (pain)c caused by ATP leaking from damaged cells, 2) rubor (redness) caused by vasodilation as a result of substancce P from nociceptors and of histamine released from mast cells, 3) tumor (swelling), caused by vasodilation, 4) calor (heat) caused by vasodilation
