Flashcards in 4 - Neuropeptides, NO, hydrogen sulfide and Purines Deck (58):
Neuropeptides are packaged into?
Neuropeptides are packaged into dense core vesicles (labelled by SEM observations).
Once neuropeptides are packaged into golgi network vesicles, what happens to the vesicles as they are processed?
The vesicles are originally large in diameter, but they are concentrated as they are processed, leading to dense core vesicles.
Corticotropin-releasing hormone (CRH) receptors?
CRH1 and CRH2 expressed in all brain structures. Regulate variety of functions and involved in anxiety, depression and stress.
Which neuropeptide receptor most involved in pain?
What do opioid receptors mostly modulate?
The brain has mostly what type of adenosine receptor?
A1 and A2A
What is caffeine's effect on the brain? (which receptors?)
Blocks adenosine purinergic receptors in the brain.
What is a neuropeptide?
A group of around 100 small peptides involved in neuronal signaling. Synthesized in ribosomes in the form of preprohormones, which are larger precursors that need to be cleaved.
True or false? Neuropeptides often coexist with classical NTs in neurons
True or false? Neuropeptides mostly act via ionotropic receptors.
False. Mostly with metabotropic receptors.
What does substance P do?
Induce intestinal contractions. First neuropeptide discovered
What polypeptide is the precursor of many neuropeptides?
What type of enzyme cleaves proopiomelanocortin (POMC) neuropeptide precursors? At what residues?
At lysine and/or arginine residues
What are the three possible melanocortin products from proopiomelanocortin cleavage?
- adrenocorticotrophin (ACTH)
- melanotrophins (MSH)
What are large granular vesicles (LGVs)?
The vesicles that neuropeptides are loaded into (also called large dense core vesicles)
How are neuropeptides packaged?
- Trans golgi network to immature large granular vesicles
- Large granular vesicles fuse to form mature LGVs
True or false?
Large granular vesicles can contain a mixture of neuropeptides
True or false? Neuropeptides co-store and co-released can exert opposing actions.
True, an example is dynorphin and hypocretin
What are tachykinin receptors?
- Bind endogenous tachykinins (substance P, neurokinin A, neurokinin)
- Involved in mediation of pain
What are angiotensin II receptors?
- Stimulates Gq protein
- Stimulates ACTH and vasopressin secretion in the pituitary
- Increases thirst and desire for salt
What are VIP (vasoactive intestinal peptide) and PACAP (pituitary adenylate cyclase-activating polypeptide) transmitters and their receptors?
VIP: VPAC1 and VPAC2 receptors
PACAP: PAC1 receptor
Show neuroprotective functions in the CNS
What is NPY1-5R receptor?
Stimulated by NPY, which is co-stored and co-released together with ATP and norepinephrine in most sympathetic axon terminals. Coupled to Gi, involved in control of circadian rhythms, anxiety and appetite.
What is somatostatin?
A neuropeptide that is widely distributed in the nervous system, and five different G-protein coupled somatostatin receptors have been cloned. Inhibits release of GH in anterior pituitary.
What happens when bombesin receptors are activated?
- Decrease feeding
- Involved in anxiety,
- Circadian rhythms
What are bradykinin receptors?
Involved in the mediation of pain, hyperalgesia and decrease in blood pressure
What are corticotropin-releasing hormone receptors involved in?
What are galanin receptors involved in?
Inhibitory effect on NT release and neuroprotective properties. Stimulates neurogenesis.
What does a Gal1 (galanin) knockout show?
What does activation of brain ghrelin receptor (GHSR) cause?
stimulation of appetite
What happens to neurotensin receptors in schizophrenic patients?
Lowered receptor density
What are neurotrophin peptide receptors associated with?
What are orexin receptors associated with?
- Sleep regulation
What do opioid receptors mediate?
How is nitric oxide synthesized?
Synthesized from L-arginine by nitric oxid synthase (NOS) in the presence of oxygen and cofactors
What are the three isoforms of NOS?
- Neuronal NO synthase
- Immunological or inducible NOS
- Endothelial NOS
What neuropeptide was initially found as epithelium-derived relaxing factor (EDRF)?
Nitric Oxide (NO)
What process of NO synthesis is calmodulin (CaM) dependent?
Synthases binding together into dimers in the oxygenase domain to make a single functional unit (homodimer).
How does NO regulate vascular smooth muscles?
- Action potential stimulates neuronal NOS to produce NO
- NO diffuses to the muscle, activating muscle soluble guanylyl cyclase
- Guanylyl cyclase converts GTP into cGMP
- cGMP acts on cGMP dependent protein kinases, phosphodiesterases and cyclic nucleotide-gated ion channels, which results in muscle relaxation
Where does nitric oxide synthase show high expression?
- Olfactory bulb
- Substantia nigra
What six behaviours does NO in the brain modulate?
- Reproductive behaviour
What neuropeptide has been involved in long term potentiation (LTP) in the hippocampus, cerebral cortex, cerebellum, amygdala and spinal cord and LTD in the cerebellum and striatum?
Nitric oxide with it's cGMP pathway
What does NO mediate in peripheral organs?
Smooth muscle relaxation
NO reacts with superoxide ions to form peroxynitrite in the brain. What is the consequence of this?
Peroxynitrite can react with proteins, lipids or DNA and break down to yield the noxious hydroxyl and nitrogen dioxide radicals, NO can also inhibit mitochondrial respiration
Inhalation of what neuropeptide can prevent brain injury in premature newborns?
How is nitric oxide used to treat erectile dysfunction?
Inhibiting phosphodiesterase 5 (PDE5) will promote cGMP degradation (decrease ability of NO to relax smooth muscle)
True or false? Hydrogen sulfide (H2S) is a gas
Where is H2S produced in a cell?
What are the actions of H2S?
- cytoprotective (prevents apoptosis)
- Dilates blood vessels
- Reduces phosphorylation and ATP biosynthesis
- Reduces oxidative stress in mitochondria and induce a suspended-animation like state (useful in hypoxia nd preservation of transplantable organs)
What are the three transmitters of the purinergic signalling system?
What are the three purinergic receptors?
- PTX receptors (ionotropic)
- PTY receptors (G protein coupled for ATP and ADP)
- P1 metabotropic adenosine receptors
What are the four adenosine receptors (P1) and where are they found?
A1 (CNS, heart)
A2a (Brain, heart, lungs)
A2b (large intestine, bladder)
A3 (lung, liver, brain)
True or false? Purinergic receptors are only expressed by neurons?
False, also expressed in glia
What are purinergic sympathetic co-transmissions?
- When ATP and norepinephrine are co-released from small granular vesicles (SGV)
- Gast contraction is mediated by ATP, which evokes excitatory junction potentials with the ionotropic P2X
- Norepinephrine induces slow contraction via activation of α1 metabotropic receptors
- Neuropeptide Y is released from large granular vesicles to presynaptically inhibit ATP/norepinephrine release
How does ATP derived adenosine (ADO) induce vasodilation?
It acts on muscular P1 receptors and also via presynaptic receptors located on the perivascular nerves
Explain purinergic mechanosensory transduction
Distension (stretching membranes) induces release of ATP from epithelium which acts on P2X sensory nerves and the signal is then sent to the CNS
What do PTY platelet receptor antagonists do?
Inhibiting blood clots in artery diseases
Selective adenosine agonists are undergoing clinical trials for?
- Cardiac arrhythmias and pain (A1)
- Cardiac imaging and inflammation (A2a)
- Colon cancer, rheumatoid arthritis, psoriasis and dry eye (A3)