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Related Concept Videos

G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Adrenergic Receptors (Adrenoceptors): Classification01:27

Adrenergic Receptors (Adrenoceptors): Classification

Adrenergic receptors, or adrenoceptors, respond to the autonomic neurotransmitter noradrenaline and other endogenous catecholamine agonists. They are classified into two main families, α and β, based on their pharmacological response and are further subdivided depending on their location, elicited response, and affinity to specific agonists or antagonists.
α-Adrenoceptors
α-Adrenoceptors are classified into two main subtypes: α1 and α2. The α1 adrenoceptors, which are found on postsynaptic...
Adrenergic Receptors: ɑ Subtype01:31

Adrenergic Receptors: ɑ Subtype

Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
Adrenergic Receptors: β Subtype01:26

Adrenergic Receptors: β Subtype

β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors have equal affinities for...
Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers01:24

Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers

Adrenergic stimulation generally impacts cardiac rate and rhythm. Specifically, stimulation of the β-adrenoceptors triggers an increase in intracellular calcium ion influx and pacemaker currents, which may cause arrhythmias. Catecholamines like adrenaline also demonstrate β2-adrenoceptor-mediated hypokalemia, impacting cardiac action potential and disrupting the normal cardiac rhythm. Class II antiarrhythmic drugs are β-adrenoceptor antagonists or β-blockers, which indirectly block calcium...
Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers01:20

Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers

Class IV antiarrhythmic drugs, such as verapamil and diltiazem, block calcium channels. They primarily affect the heart, slowing the conduction in calcium-dependent tissues like the SA and AV nodes. These drugs manage reentrant supraventricular tachycardia (SVT) and reduce ventricular rate in atrial flutter/fibrillation.
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...

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Use of a Hanging Weight System for Coronary Artery Occlusion in Mice
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Distinct cardioprotective effects of adenosine mediated by differential coupling of receptor subtypes to

M Parsons1, L Young, J E Lee

  • 1Department of Medicine, Cardiovascular Division, University of Pennsylvania Medical Center, Philadelphia 19104, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|July 6, 2000
PubMed
Summary

Adenosine receptors A(1) and A(3) protect the heart during ischemia. Activating both receptors enhances cardioprotection, suggesting combined agonists for treating myocardial ischemia.

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Area of Science:

  • Cardiology
  • Molecular Pharmacology
  • Cell Signaling

Background:

  • Adenosine plays a crucial role in cardiac protection during ischemia.
  • Adenosine receptor subtypes A(1) and A(3) mediate these protective effects.
  • Understanding the specific signaling pathways is key to developing therapeutic strategies.

Purpose of the Study:

  • To characterize the signaling pathways activated by adenosine A(1) and A(3) receptors in cardioprotection against ischemia.
  • To investigate the distinct roles of A(1) and A(3) receptor activation.
  • To evaluate the combined effect of stimulating both receptor subtypes.

Main Methods:

  • Utilized a chick embryo ventricular myocyte culture model for ischemia-induced injury.
  • Employed selective agonists for adenosine A(1) and A(3) receptors.
  • Investigated phospholipase C and D activation.
  • Used transfected atrial myocytes to confirm A(3) receptor specificity.

Main Results:

  • Selective A(1) receptor agonists activated phospholipase C.
  • Selective A(3) receptor agonists activated phospholipase D.
  • A(3) receptor-phospholipase D interaction was specific, confirmed in transfected cells.
  • Co-activation of endogenous A(1) and A(3) receptors yielded synergistic cardioprotection.

Conclusions:

  • Adenosine A(1) and A(3) receptors activate distinct signaling pathways (PLC and PLD, respectively) for cardioprotection.
  • Combined activation of adenosine A(1) and A(3) receptors provides superior protection against ischemia compared to individual receptor stimulation.
  • Dual agonists targeting both adenosine A(1) and A(3) receptors show promise for treating myocardial ischemia.