Calcium, Nitric Oxide, Autacoids & Autonomic Pharmacology

Vocabulary flashcards covering key terms, proteins, receptors, enzymes, drugs and pathological concepts from the lecture notes on calcium signalling, nitric oxide, eicosanoids, and autonomic pharmacology.

Calcium signalling

Intracellular communication system relying on steep Ca2+ gradients between extra- and intracellular compartments to trigger diverse cellular processes.

Plasma Membrane Ca2+-ATPase (PMCA)

High-affinity, low-capacity ATP-driven pump that continuously extrudes Ca2+ from the cytosol; activated by Ca2+-calmodulin.

Na+/Ca2+ Exchanger (NCX)

Low-affinity, high-capacity transporter that removes 1 Ca2+ in exchange for 3 Na+; rapidly restores Ca2+ after large transients.

Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase (SERCA)

ATP-powered pump that returns cytosolic Ca2+ into the sarcoplasmic or endoplasmic reticulum (2 Ca2+ per ATP).

Ryanodine receptor (RyR)

SR Ca2+ release channel activated mechanically in skeletal muscle or by Ca2+ itself in cardiac CICR.

Inositol-1,4,5-trisphosphate receptor (IP3R)

SR/ER channel that releases Ca2+ when bound by IP3 generated by PLC-β/γ signalling.

Store-Operated Calcium Channel (SOCC)

Plasma-membrane Ca2+ entry pathway opened when SR Ca2+ stores are depleted; composed of STIM1 sensor and ORAI1 pore.

STIM1

ER Ca2+ sensor that activates ORAI1 channels when luminal Ca2+ is low.

ORAI1

Plasma-membrane pore subunit of SOCCs permitting Ca2+ influx after STIM1 activation.

Calcium-induced calcium release (CICR)

Process in cardiac & smooth muscle where a small Ca2+ influx via DHPR triggers massive RyR-mediated SR Ca2+ release.

Dihydropyridine receptor (DHPR)

Voltage-gated L-type Ca2+ channel; mechanically couples to RyR in skeletal muscle and initiates CICR in heart.

Calcium-calmodulin (Ca-CaM)

Ca2+-binding complex that activates PMCA, kinases and phosphatases to propagate Ca2+ signals.

Calcium excitotoxicity

Cell damage from prolonged high cytosolic Ca2+, generating ROS and triggering apoptosis via cytochrome c.

Verapamil

Non-dihydropyridine L-type Ca2+ channel blocker used for hypertension and arrhythmias.

Diltiazem

Non-dihydropyridine Ca2+ antagonist that reduces cardiac conduction and vascular tone.

Nitric oxide (NO)

Gaseous autacoid formed from L-arginine by NOS; activates sGC→cGMP→PKG leading to smooth-muscle relaxation.

NOS1 (nNOS)

Constitutive, Ca2+-dependent neuronal/muscle NOS working at nanomolar Ca2+ to modulate neurotransmission & metabolism.

NOS2 (iNOS)

Inducible, Ca2+-independent NOS expressed during inflammation; produces large NO amounts for macrophage cytotoxicity.

NOS3 (eNOS)

Endothelial, Ca2+-dependent NOS that generates NO for vasodilation; activated by AKT-PKB signalling.

Soluble guanylate cyclase (sGC)

Cytosolic enzyme stimulated by NO to convert GTP to cGMP.

cGMP-dependent protein kinase (PKG)

Kinase activated by cGMP that phosphorylates targets including MLCK to relax smooth muscle.

Nitroglycerin

NO-donating drug used acutely for angina; dilates capacitance veins to lower cardiac preload.

Nebivolol

β1-blocker with NO-mediated vasodilatory properties.

Riociguat

sGC stimulator increasing cGMP; treats pulmonary hypertension and reperfusion injury.

Autacoids

Locally acting endogenous mediators with short half-life, e.g., eicosanoids, NO, histamine.

Eicosanoids

20-carbon fatty-acid derivatives (prostanoids + leukotrienes) formed from arachidonic acid.

Cyclo-oxygenase-1 (COX-1)

Constitutive enzyme converting arachidonic acid to PGH2; supplies housekeeping prostanoids (TXA2, gastric PGs).

Cyclo-oxygenase-2 (COX-2)

Inducible isoform up-regulated by inflammation; source of inflammatory prostaglandins & PGI2.

Prostaglandin I2 (PGI2)

Vasodilatory, cardioprotective prostacyclin produced mainly via COX-2.

Thromboxane A2 (TXA2)

Platelet-derived vasoconstrictor and aggregator formed via COX-1.

Leukotrienes

5-LOX products mediating bronchial inflammation; cysteinyl-LTs elevated in asthma.

Non-steroidal anti-inflammatory drugs (NSAIDs)

COX inhibitors providing anti-inflammatory, antipyretic, analgesic and (COX-1) antiplatelet effects.

Aspirin (acetyl-salicylic acid)

Irreversible COX-1 inhibitor used as antiplatelet agent; risk of Reye’s syndrome in children.

Paracetamol (acetaminophen)

Analgesic/antipyretic NSAID with weak anti-inflammatory action; overdose causes NAPQI-mediated hepatotoxicity.

Celecoxib

Selective COX-2 inhibitor that spares gastric PGs but may increase CV risk.

Zileuton

5-lipoxygenase inhibitor that reduces leukotriene synthesis in asthma.

Montelukast

CysLT1 receptor antagonist used for leukotriene-mediated asthma control.

Adrenergic receptor α1

Gq-coupled receptor; activation causes PLC→IP3/DAG→Ca2+ rise, smooth-muscle contraction and vasoconstriction.

Adrenergic receptor α2

Gi-coupled receptor on presynaptic terminals; inhibits adenylyl cyclase and NE release (autoreceptor).

Adrenergic receptor β1

Gs-coupled receptor in heart & JG cells; increases cAMP for positive inotropy, chronotropy, renin release.

Adrenergic receptor β2

Gs-coupled receptor in smooth muscle; cAMP/PKA phosphorylates MLCK → relaxation, bronchodilation, vasodilation.

Dobutamine

β1-selective sympathomimetic used for acute heart failure to increase cardiac output.

Adrenaline (epinephrine)

Endogenous catecholamine acting on α1/2 and β1/2; used for anaphylaxis (vasoconstriction & bronchodilation).

Noradrenaline (norepinephrine)

Catecholamine with α1/2 & β1 activity (no β2); raises peripheral resistance in shock.

Dopamine

Dose-dependent catecholamine: D1 renal vasodilation (low), β1 inotropy (mod), α1 vasoconstriction (high).

Clonidine

Central α2-agonist antihypertensive; withdrawal may cause rebound hypertension.

Guanfacine

α2-agonist used for ADHD by enhancing prefrontal cortical regulation.

Salbutamol (albuterol)

Short-acting β2-agonist bronchodilator for asthma (Ventolin).

Mirabegron

β3-agonist that relaxes detrusor muscle to treat overactive bladder.

Ephedrine

Mixed indirect sympathomimetic that releases NE and directly stimulates receptors; decongestant.

Tyramine

Dietary monoamine that displaces NE; dangerous with MAO inhibitors → hypertensive crisis.

Doxazosin

Selective α1-antagonist used for hypertension and benign prostatic hyperplasia.

Yohimbine

Selective α2-antagonist increasing sympathetic tone; treats orthostatic hypotension.

Propranolol

First-generation non-selective β-blocker; contraindicated in asthma due to β2 blockade.

Metoprolol

Second-generation β1-selective blocker; manages angina, heart failure, hypertension.

Timolol

Non-selective β-blocker applied topically to decrease aqueous humour in glaucoma.

Reserpine

Indirect adrenergic antagonist that depletes NE by inhibiting vesicular storage.

Guanethidine

Adrenergic neuron blocker replacing NE in vesicles; lowers blood pressure.

Parasympathetic nervous system

Autonomic division with long pre- and short postganglionic fibers using ACh at nicotinic (Nn) and muscarinic receptors.

Acetylcholine (ACh)

Primary parasympathetic neurotransmitter synthesised by choline acetyltransferase; degraded by acetylcholinesterase.

Nicotinic receptor (Nn)

Ligand-gated ion channel on autonomic ganglia; fast synaptic transmission.

Nicotinic receptor (Nm)

Neuromuscular junction ion channel mediating skeletal-muscle contraction.

Muscarinic receptor M1

Gq-coupled receptor in CNS and gastric glands; modulates cognition and acid secretion.

Muscarinic receptor M2

Gi-coupled cardiac receptor; slows heart rate and conduction (vagal tone).

Muscarinic receptor M3

Gq-coupled receptor in smooth muscle & endothelium; triggers bronchoconstriction, gland secretion, NO-mediated vasodilation.

Pilocarpine

Direct muscarinic agonist used topically for glaucoma by increasing aqueous humour outflow.

Bethanechol

Resistant choline ester muscarinic agonist treating urinary retention and GI atony.

Neostigmine

Reversible acetylcholinesterase inhibitor used for myasthenia gravis and to reverse NMJ blockade.

Physostigmine

Tertiary AChE inhibitor that crosses BBB; antidote for anticholinergic toxicity.

Organophosphates

Irreversible AChE inhibitors (nerve agents & pesticides) causing cholinergic crisis; treated with atropine + pralidoxime.

Atropine

Non-selective muscarinic antagonist causing mydriasis, anti-secretory and cardiostimulant effects.

Scopolamine

Muscarinic antagonist used for motion-sickness prophylaxis (transdermal patches).

Ipratropium

Inhaled quaternary muscarinic antagonist (M3) providing bronchodilation in COPD/asthma.

Pirenzepine

Selective M1 antagonist formerly used to reduce gastric acid secretion.

Benztropine

Central muscarinic antagonist used to treat Parkinsonian tremor and antipsychotic-induced EPS.

Scopolamine-N-butyl-bromide (Buscopan)

Peripheral quaternary muscarinic antagonist relieving GI spasms.

Nicotine (high dose)

Ganglionic blocker producing autonomic paralysis by persistent Nn activation and desensitisation.

Succinylcholine

Depolarising neuromuscular blocker causing transient fasciculation then flaccid paralysis; degraded by pseudocholinesterase.

Curare (d-tubocurarine)

Prototype non-depolarising Nm antagonist producing skeletal-muscle relaxation during anaesthesia.

Pseudocholinesterase deficiency

Genetic absence of enzyme leading to prolonged apnea after succinylcholine administration (idiosyncratic reaction).

Reye’s syndrome

Fulminant hepatic encephalopathy in children taking aspirin during viral illness.

NAPQI

Hepatotoxic metabolite of paracetamol detoxified by glutathione; accumulates in overdose.

5-lipoxygenase (5-LOX)

Enzyme converting arachidonic acid to leukotriene precursors (LTA4).

Hypoxia-inducible factor-1α (HIF-1α)

Transcription factor stabilised when NO outcompetes O2 at cytochrome c, inducing hypoxic gene expression.

Asymmetric dimethylarginine (ADMA)

Endogenous L-arginine analogue that competitively inhibits NOS activity.

Calcium signalling

Intracellular communication system relying on steep Ca2+ gradients between extra- and intracellular compartments to trigger diverse cellular processes.

Plasma Membrane Ca2+-ATPase (PMCA)

High-affinity, low-capacity ATP-driven pump that continuously extrudes Ca2+ from the cytosol; activated by Ca2+-calmodulin.

Na+/Ca2+ Exchanger (NCX)

Low-affinity, high-capacity transporter that removes 1 Ca2+ in exchange for 3 Na+; rapidly restores Ca2+ after large transients.

Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase (SERCA)

ATP-powered pump that returns cytosolic Ca2+ into the sarcoplasmic or endoplasmic reticulum (2 Ca2+ per ATP).

Ryanodine receptor (RyR)

SR Ca2+ release channel activated mechanically in skeletal muscle or by Ca2+ itself in cardiac CICR.

Inositol-1,4,5-trisphosphate receptor (IP3R)

SR/ER channel that releases Ca2+ when bound by IP3 generated by PLC-β/γ signalling.

Store-Operated Calcium Channel (SOCC)

Plasma-membrane Ca2+ entry pathway opened when SR Ca2+ stores are depleted; composed of STIM1 sensor and ORAI1 pore.

STIM1

ER Ca2+ sensor that activates ORAI1 channels when luminal Ca2+ is low.

ORAI1

Plasma-membrane pore subunit of SOCCs permitting Ca2+ influx after STIM1 activation.

Calcium-induced calcium release (CICR)

Process in cardiac & smooth muscle where a small Ca2+ influx via DHPR triggers massive RyR-mediated SR Ca2+ release.

Dihydropyridine receptor (DHPR)

Voltage-gated L-type Ca2+ channel; mechanically couples to RyR in skeletal muscle and initiates CICR in heart.

Calcium-calmodulin (Ca-CaM)

Ca2+-binding complex that activates PMCA, kinases and phosphatases to propagate Ca2+ signals.

Calcium excitotoxicity

Cell damage from prolonged high cytosolic Ca2+, generating ROS and triggering apoptosis via cytochrome c.

Verapamil

Non-dihydropyridine L-type Ca2+ channel blocker used for hypertension and arrhythmias.

Diltiazem

Non-dihydropyridine Ca2+ antagonist that reduces cardiac conduction and vascular tone.