It is a specific protein that is the site for binding of a signaling molecule. Can also be: Enzymes , Na+ , K+ ATPase pump , nucleic acids Two types Transmembrane Intracellular (some nucleic)

Is a compound that is specific fo each receptor Activates the receptor causing biological response Endogenous substances

A compound that binds to a receptor causing activation and EXPECTED effect Effect can be natural or synthetic Two main types: Full Partial

A drug that binds to a receptor (usually at agonist site) that activates the receptor, but not as much as a full agonist. When a partial agonist is administered with a full agonist, drug effect of full agonist is decreased Partial agonist can have antagonistic activity: agonist- antagonist Occupy the same number of receptors as full agonist, but effect is decreased

A compound that binds to the receptor creating OPPOSITE of expected effect Binds to same sites as agonist (competing with it) " Turns off " activity of the receptor \ It is NOT an ANTAGONIST

A compound that when bound to a receptor causes INACTIVATION , preventing expected ( normal ) response. Usually reversible Two Types: Competitive Noncompetitive When ligand is bound Interact with receptor but DO NOT CHANGE receptor Have affinity but NO EFFICACY Block the action of other drugs Effect observed ONLY IN THE PRESENCE OF AGONIST

Do not have a net charge, but certain regions have partial negative and positive charge Soluable in H2O--water is polar

Receptors Flashcards by Jenna Welch

What is a receptor?

It is a specific protein that is the site for binding of a signaling molecule.

Can also be: Enzymes, Na⁺, K⁺ ATPase pump, nucleic acids
Two types
- Transmembrane
- Intracellular (some nucleic)

How well did you know this?

Not at all

Perfectly

Ligand

Is a compound that is specific fo each receptor

Activates the receptor causing biological response
Endogenous substances

How well did you know this?

Not at all

Perfectly

Agonist

A compound that binds to a receptor causing activation and EXPECTED effect

Effect can be natural or synthetic
Two main types:
- Full
- Partial

How well did you know this?

Not at all

Perfectly

Partial Agonist

A drug that binds to a receptor (usually at agonist site) that activates the receptor, but not as much as a full agonist.

When a partial agonist is administered with a full agonist, drug effect of full agonist is decreased
Partial agonist can have antagonistic activity: agonist- antagonist
Occupy the same number of receptors as full agonist, but effect is decreased

How well did you know this?

Not at all

Perfectly

Inverse Agonist

A compound that binds to the receptor creating OPPOSITE of expected effect

Binds to same sites as agonist (competing with it)
“Turns off” activity of the receptor

*It is NOT an ANTAGONIST

How well did you know this?

Not at all

Perfectly

Antagonist

A compound that when bound to a receptor causes INACTIVATION, preventing expected (normal) response.

Usually reversible
Two Types:
- Competitive
- Noncompetitive
  - When ligand is bound
Interact with receptor but DO NOT CHANGE receptor
Have affinity but NO EFFICACY
Block the action of other drugs
Effect observed ONLY IN THE PRESENCE OF AGONIST

How well did you know this?

Not at all

Perfectly

Competitive Antagonist

COMPETES with AGONIST for receptor binding sites

Concentration and receptor affinity affect response
Can reverse the effects of ANtagonist with large dose of AGONIST

How well did you know this?

Not at all

Perfectly

Noncompetitive Antagonist

Binds to receptor at DISCRETE SITES [allosteric] (different from Agonist) and alters maximal response

Partial Response: Decreases maximum efficacy of drug

How well did you know this?

Not at all

Perfectly

Receptor States

Multiple receptors in the cell and they change in number

Not all receptors are active or inactive

Agonist–Fully Active
Partial Agonist–Some Active
Antagonist–Changes balance so receptor is inactive
- “active” but blocked
Inverse Agonist–Favors inverse of full agonist
- acts as antagonist

How well did you know this?

Not at all

Perfectly

Agonists

Antagonists

AGONIST:

Enzyme activation/Inhibition

Ion channel modulation

DNA transcription

ANTAGONIST:

Effect of Agonist blocked

How well did you know this?

Not at all

Perfectly

Non-Polar Molecule

A molecule that has a neutral charge; no net positive or negative charge

How well did you know this?

Not at all

Perfectly

Polar Molecule

Do not have a net charge, but certain regions have partial negative and positive charge
- Soluable in H2O–water is polar

How well did you know this?

Not at all

Perfectly

Occurs in the absence of a ligand. Cell will increase the number of receptors in an attempt to sense missing ligand

Up-Regulation

How well did you know this?

Not at all

Perfectly

Occurs with increase stimulation by a ligand. Cell will reduce the number of receptors specific to that ligand.

Down-Regulation

How well did you know this?

Not at all

Perfectly

Name the four types of cell receptors.

Ion channel linked
G-protein coupled
Intrinsic enzyme linked
Intracellular

How well did you know this?

Not at all

Perfectly

Respond to fast neurotransmitters such as Ach.
Nicotinic and glutamate receptors (Excitatory)
GABA_a and glycine receptors (Inhibitory)

Ligand-gated Ion Channel

How well did you know this?

Not at all

Perfectly

Present in the membranes of excitable nerves, cardiac, and skeletal muscle cells
Open/Close in response to voltage changes in cell
Named for ion permeability
Play an important role in muscle contraction/propagation of action potentials
Some excitatory, some inhibitory
Local anesthetics bind to the intracellular domain of this receptor

Voltage-gated ion Channel

How well did you know this?

Not at all

Perfectly

Cellular response illicited with these receptors through protein that stimulates an increase or decrease in protein synthesis. (Ex: Catecholamines)
Most numerous receptor type
Contains three subunits that influence enzyme activity and ion channels

G-Protein Coupled Receptors

How well did you know this?

Not at all

Perfectly

Subunit that stimulates, increases adenylcyclase, makes cAMP from ATP.
- cAMP is important 2nd messenger

G_s

Protein Subunit

How well did you know this?

Not at all

Perfectly

Subunit that inhibits Adenylcyclase

G_{<span>i</span>}

Protein Subunit

How well did you know this?

Not at all

Perfectly

Activates phospholipase C, increasing DAG and IP₃, which increases Ca²⁺ from cells

G_q

Protein Subunit

How well did you know this?

Not at all

Perfectly

Prolonged exposure of a receptor to an agonist causing subsequent dosing with agonist to produce reduced maximal effects.

–Barash Chpt 11, pg 254

Desensitization

How well did you know this?

Not at all

Perfectly

Prolonged exposure of receptors to antagonist.

Can occur with long term use of beta-blockers and abrupt discontinuation.

Hypersensitization

How well did you know this?

Not at all

Perfectly

Associated with sypathetic response of the autonomic nervous system (ANS)
Located in CNS and peripheral tissues
Characterized by neurotransmitter response
- Epi, Norepi, Dopamine
Largely excitatory response; Fight or Flight

Adrenergic Receptor

How well did you know this?

Not at all

Perfectly

Name the three major subtypes of Adrenergic Receptors.

1. Alpha 2. Beta (ß) 3. Dopaminergic (D or DA)

* Receptors located in *vascular smooth mm, GU smooth mm, the liver,* and *CNS **post-synaptically** (excitatory*) * Activation causes contsriction of smooth mm (vasoconstriction) and positive inotropism in the myocardium * GPCR * _**G_q** subunit_ - activates phospolipase C, increasing DAG and IP₃

*Alpha-1* Adrenergic Receptors

Alpha-1 Adrenergic *Agonists*

* Phenylepherine, Norepinepherine, Epinepherine, Dopamine * Causes smooth mm contraction, vasoconstriction, antidiuresis; increases IP₃ and DAG

Alpha-1 Adrenergic *ANtagonists*

* Phenoxybenzamine, phentolamine (Regitine-used as a "reversal" for Epi, NE infiltration in PIV), Labetalol, Doxazosin (Cardura), Prazosin (Minipress) * Vasodilation, relaxation of smooth mm

* Receptors located in *pancreatic islet (ß) cells, platelets, nerve terminals, CNS,* and *vascular smooth mm* * ***Presynaptic*** activation decreases cAMP which inhibits NE release, resulting in decreased SVR, decreased CO, decreased inotropism, and decreased HR * ***Postsynaptic*** activation causes vasoconstriction and platelet aggregation * GPCR * _**G_i** subunit_ - Inhibits adenylate cyclase, Ca⁺ and K⁺ ion channels.

*Alpha-2* Adrenergic Receptors

Alpha-2 Adrenergic ## Footnote *Agonists*

* *Clonidine*, NorEpi, Epi, Phenylepherine * **Presynaptically**: Clonidine; dexmedetomidine (Precedex) * Reduced Peripheral Vascular Resistance (PVR) * Inhibit release of NorEpi * CNS depression, Sedation * **Postsynaptically**: NorEpi, Phenylepherine, Epi * Vasoconstriction * Inhibition of insulin release, decreased GI motility, inhibition of ADH, platelet aggregation

Alpha-2 Adrenergic ## Footnote *Antagonists*

* Rarely used medically * Similar to Alpha-1 Antagonists-inhibit release of NE

* Receptors located in the heart (SA node, myocardium, ventricular conduction system) and renal juxtaglomerular cells * Activation increases cAMP * Increased HR, positive inotropic and chronotropic effects, renal renin release, relaxed coronaries * **Postsynaptic**, sensitive to NE and Epi equally * GPCR * **_G_s_** **_subunit_** - stimulates adenylate cyclase and Ca⁺ ion channels

*Beta (ß)-1* Adrenergic Receptors

Beta (ß)-1 Adrenergic *Agonists*

* Isoproterenol, Epi, NorEpi, Dopamine, Dobutamine * Increased HR, Increase contractility

Beta (ß)-1 Adrenergic *Antagonists*

* Commonly called "Beta-Blockers" * Sudden cessation can elicit rebound tachycardia and myocardial ischemia r/t upregluation of B-1 receptors * Metoprolol, Propanolol, Esmolol * **Postsynaptic**: *Vasodilation, decreased HR, decrease inotropy*

* Receptor located: * **presynaptically** in the myocardium and SA node * **postsynaptically** in vascular, bronchial, GI, and GU smooth mm * Activation increases cAMP: * Sensitive to _NE_ *presynaptically:* * ** constriction, accelerated NE release * **_Epi_** ***postsynaptically**:* * **Positive inotropism, chronotriopism, dialation of smooth mm * **_G_s subunit_** - Stimulates adenylate cyclase and Ca⁺ ion channels

Beta (ß)-2 Adrenergic Receptor

Beta (ß)-2 Adrenergic *Agonists*

* Commonly used for bronchodilatory effects * Isoproterenol (used for bronchospasm during anesthesia), Albuterol (SABA), Epi, NE, Dopamine * *Presynaptic*: Increased HR, accelerates NE release * **Postsynaptic:** Vasodilation, bronchodilation, Gi and GU relaxation, uterine relaxation, insulin secretion, amylase secretion

Beta (ß)-2 Adrenergic *Antagonists*

* ß2 receptors are typically antagonized with nonselective ß1 Blockers * Butoxamine (selective--used primarly in experimentation to identify ß2 receptors), Propanolol, Alprenolol (antihypertensive/angina med; older med), Esmolol, Nadolol, Timolol, Labetolol * small degree of peripheral vascular bed vasoconstriction occurs with selective antagonism

* Receptors located within the *CNS, vascular smooth mm, kidneys, and postganglionic sympathetic nerves* * Has 5 subtypes, two of which are predominant * GPCR

Dopaminergic Receptors

* Receptors located in vascular smooth mm, renal and mesentery BV, rental tubules, juxtaglomerular cells, and sypathetic ganglia * Similar in structure to subtype 5, but located in different areas. * Activation increases cAMP: * **Postsynaptic:** * Vasodilation, diuresis, renin release, sodium excretion, minor inhibition of sypathetic ganglial nerves * GPCR * **_G_s subunit_** - stimulates adenylate cyclase and Ca⁺ ion channels

*Dopamine (DA,D)₁* Receptor

DA₁ ## Footnote *Agonists*

* Fenoldopam, Dopamine, Epi * Vasodilation, diuresis, nausea, vomiting, dizziness

DA₁ ## Footnote *Antagonist*

* Haloperidol, Droperidol, Phenothiazines (Thorazine), Metoclopramide (Reglan) * Relief of n/v (Reglan, Haloperidol, Droperidol), increased gastric motility (Reglan), mesenteric smooth mm constriction,

* Receptor located in presynaptic postganglionic sympathetic nerves and postsynaptic renal and mesenteric vascular smooth mm. * Similar in structure to subtypes 3 and 4 * Activation decreases cAMP * **Presynaptic**: inhibition of NE, secondary vasodilation * **Postsynaptic**: vasoconstriction, inhibition of aldosterone relase from adrenal cortex * GPCR * **_G_i subunit_** - inhibits adenylate cyclase, Ca⁺ and K⁺ ion channels

*Dopamine (DA,D)₂* Receptor

DA₂ ## Footnote *Agonists*

* Dopamine, Bromocriptine * **Presynaptic**: * Inhibition of NE release, secondary vasodilation * **Postsynaptic**: * Vasoconstriction of renal and mesenteric vasculature

DA₂ ## Footnote *Antagonists*

* Domperidone * GI prokinesis, prolactin release, antiemetic effects

* Associated with the parasympathetic region of the CNS, Rest and Digest * Has excitatory and inbitory, * Two main types: * Nicotinic * Muscarinic

Cholinergic Receptors

* *Ligand-gated ion channel receptors* * Two subtypes * *m* - found in postsynaptic skeletal neuro*muscular* junction * *n* - found in the autonomic *ganglia* (postganglionic; ANS) and adrenal medulla * Activated by Acetycholine, opening Na⁺ and K⁺ depolarizing ion channel * action mediated by ion

Nicotinic Cholinergic Receptor

Nicotinic ## Footnote *Agonists*

* Acetycholine, Nicotine * Nn and Nm * **Succinylcholine** * **Nm** : *depolarizing NMB*, opens ligand ion channel, depolarizing and inhibiting neurotranmission

Nicotinic ## Footnote *Antagonists*

* ***Nn*** * Dextromethorphan * Trimethaphan - inhibits sympathetic and parasympathetic autonomic activity, used for BP control in aortic dissection * vasodilation * ***Nm*** * **Vecuronium** - competitive antagonist, blocks Ach at the NM junction; muscle relaxation, paralysis. * Rocuronium, Cisatracurium (Nimbex)

* *G-protein coupled receptor* * Has 5 subtypes * **1,3,5** - **G_q subunit**: activates Phospholipase C, increasing DAG and IP₃ * 1 - present in CNS, *autonomic ganglia, glands (salivary, gastric)*, enteric GI nerves * 3 - present in *CNS, smooth mm*, and glands * 5 - low levels in CNS, associated with Dopamine neurons * **2, 4** - **G_i subunit**: inhibits adenylate cyclase * 2 - present in CNS, *heart*, smooth mm, and autonomic nerve terminals * 4 - present in CNS, forebrain

Muscarinic Cholinergic Receptors

Muscarinic ## Footnote *Agonists*

* Acetycholine * Muscarine * Toxic compound in mushrooms * Increased salivation, gastric secretions (M1), decreased HR and atrial contractility (M2), smooth mm contraction, emesis (M3)

Muscarinic ## Footnote *Antagonists*

* Scopolamine * antiemetic properties, reduces secretions * Atropine * broad antagonist * reduces secretions, increases HR and atrial contractility

* Two main types of these receptors * A type - found primarily in the CNS * B type - found mainly in peripheral tissue * **Postsynaptic** inhibitory receptor * A type - CNS depression * B type - skeletal muscle relaxation * GPCR

GABA receptors

GABA_A ## Footnote *Agonists*

* Act on GABA_A receptor through potentiation, direct gating and inhibition * Benzodiazepines * Propofol * Etomidate * volitile anesthetics * anesthetic steroids

GABA_A ## Footnote *Antagonists*

* Flumazenil (Romazicon) - competative antagonist

GABA_B ## Footnote *Agonists*

* Baclofen * antispasmotic * peripheral smooth mm relaxant

GABA_B ## Footnote *Antagonists*

* Saclofen * competative antagonist * used in research

* a member of the Serotonin receptor family * *ligand gated ion channel* receptor * targeted for the management of drug induced n/v * antiemetics (Zofran) antagonize * can potentiate a midgraine; migraine meds are serotonin receptor agonists * agonized response n/v

5-HT₃ Serotonin Receptor

* Receptors located on nerve endings of sensory neurons in spinal cord and in the brain on descending neurons * Three types * Mu * Kappa * Delta * When activated, decending neurons release NE and 5HT, the release of Substance P and glutamate is reduced creating less neurotranmission to brain = brain interprets less pain * GPCR * **_G_i subunit_** - inhibition of adenylate cyclase, reduction of cAMP

Opioid Receptors

* Has different subtypes * *subtype 2 associated with physical dependence* * Responsible for analgesia in spinal and supraspinal areas * specifically substantia gelatinosa in posterior horn of spinal cord * brain areas responsible for pain interpretation * Most lipophilic receptor * Activation elicits: * *Analgesia, euphoria, miosis, bradycardia, hypothermia, urinary retention, depression of ventilation, constipation*

*Mu* Opioid Receptor (MOR)

Mu ## Footnote *Agonists*

* Endorphins, Morphine, Synthetic opioids * Analgesic effect, euphoria, miosis, bradycardia, hypothermia, urinary retention, decreased GI motility (Mu₂), respiratory depression (Mu₂), physical dependence (Mu₂)

* Responsible for analgesia spinal and supraspinal * dorsal horn of spinal cord * same areas as Mu * Activation results in inhibition of neurotransmitter release via N-type Ca⁺ ion channels. * *Analgesia, sedation, dysphoria, miosis, diuresis, low abuse potential* * *Opioid agonist-antagonists* act principally on this receptor * Extensive research conducted on antagonists to combat addiction

*Kappa* Opioid Receptor (KOR)

Kappa *Agonists*

* Dynorphins * endogenous opioid peptide * Analgesic effect spinal, supraspinal, dysphoria, sedation, pupillary constriction, diuresis, low abuse potential

* Responsible for supraspinal and spinal analgesia * No current drugs on the market targeting receptor * Respond to endogenous ligands: *enkephalins* * May modulate activity of Mu receptors * Activation causes modulation of hormone and neurotransmitter release: * Analgesia, respiratory depression, physical dependence, mild constipation, urinary retention

*Delta* Opioid Receptor (DOR)

Delta *Agonists*

* Enkephalins * No drugs on market * Spinal and supraspinal analgesia, moderation of Mu receptors, respiratory depression, mild constipation, urinary retention, physical dependence

Opioid Receptor (MOR, KOR, DOR) *Antagonists*

* Naloxone (Narcan) * Competative antagonist * increases sympathetic nervous system activity * tachypnea, tachycardia, hypertension, nausea, vomiting, sudden perception of pain * Naltrexone * similar to Naloxone, but has sustained antagonism up to 24h * reduces euphoric effect * highly effective orally * Nalmefene * pure opioid antagonist * analogue of naltrexone * same potency as Naloxone * Methylnaltrexone * active at peripheral opioid receptors * ionized, does not cross blood-brain barrier

Receptors Flashcards

(65 cards)