Overview of ANS week 1 PART 2 Flashcards
Where are NN (nicotinic neuronal) receptors located? What is the result of ACh binding to these receptors?
Where are NM (nicontic muscle) receptors located? What is the result of ACh binding to these receptors?
Nicotinic receptors fall into two major subtypes
a. Nn receptors are found on neurons (Nn for nicotinic neuron) and are the type of receptors found in chain ganglia as well as in the CNS. They are ionotropic receptors that enhance Na+ channel conductance.
b. Nm receptors are found in muscle effector sites and are the traditional receptor located at the neuromuscular junction (Nm formuscle). It is also a Na+ ionotropic receptor.
What are the effects of ACh binding to M1, M3, and M5 muscarinic receptors? Where are they located?
What are the effects of ACh binding to M2 and M4 receptors? Where are these receptors located?
Muscarinic receptors fall into 5 major subtypes in two functional families. They are all metabotropic receptors.
M1, (slow EPSE in post-ganglionic fibers) M3 (most PANS effectors) and M5 are all Gq (Gq activates PLC) receptors and enhance intracellular Ca++ and regulate IP3 and diacyl-glycerol (DAG). They have various distributions. Pathway: ACh binds to M1, M3, and M5 receptor–>Gq activated—>Phospholipase C (PLC) activated–> Cleavage of phosphoinositol (PIP2)—> DAG and IP3 formed. DAG activated Protein kinase C. IP3 releases Ca2+
b. M2 (heart) and M4 are both Gi (Adenylyl cyclase–> decreased cAMP–> decreased PKA) receptors open K+ channels, reduce Ca++ and inhibit adenylyl cyclase. They are found mostly in the myocardium and CNS.
What are the effects of NE/E binding on alpha 1 receptors? Where are alpha 1 receptors located?
What are the effects of NE/E binding to alpha 2 receptors? Where are alpha 2 receptors located?
Alpha1 receptors are the traditional post-synaptic receptor that induces smooth muscle contraction (vascular smooth muscle, GI tract) and has several functions within the CNS as well. Its second messenger transducer is similar to the M1 functional family in that it increases intracellular Ca++ and regulates IP3 and DAG.
Alpha2 receptors are the classic autoreceptor that reduce future release of NE, although they are also located on post-synaptic membranes, esp. in the CNS. Also found in vascular smooth muscle, pancreas. They inhibit adenylyl cyclase-Gi
What are the effects of NE/E binding to B1, 2, and 3 receptors? Where are these receptors located?
Beta receptors exist in three major variants that have different distributions and functions.
a. Beta-1 enhances adenylyl cyclase activity and exists on a number of target sites including heart as well as on pre-synaptic ACh terminals-(heteroreceptors to decrease ACh release)
b. Beta-2 similarly enhances adenylyl cyclase, but can activate Gi. It predominantly affects smooth muscle with some cardiac effect.
c. Beta-3 similarly enhances adenylyl cyclase, especially in lipocytes.
Define the following terms:
direct acting agonists
direct acting antagonists
indirect acting agonists
indirect acting antagonists
1) direct-acting agonists, have affinity for the receptor as well as efficacy and can possess receptor subtype specificity.
2) direct-acting antagonists possess affinity for a receptor but no efficacy and can possess receptor subtype specificity.
3) indirect-acting agonists have no affinity for the receptor, but possess efficacy and do NOT possess receptor subtype specificity.
4) indirect-acting antagonists neither possess affinity nor efficacy at the receptor and do NOT possess receptor subtype specificity.
cholinergic link hypothesis
The cholinergic link hypothesis was an early hypothesis surrounding cardiac regulation and suggested that release of ACh inhibited the function of NE through heteroreceptors located on SANS terminals. Today we know this to be true and the concept has been generalized to most ANS systems. We know that activation of PANS inhibits SANS at the effector sites of many structures (e.g., bladder). However, the reverse is also true. Thus, activation of SANS can also reduce PANS activity at effector sites. Thus, in addition to central integration where SANS and PANS are mutually inhibitory to emphasize a predominant tone, activation of one system in at the effector site also inhibits the effects of the other ANS system.
What is the predominant ANS tone in each of the following organs?
heart
GI tract
bladder
vascular tone
sweat glands
In the heart, the predominant tone is PANS. Stimulation of the vagus slows down the heart more so than the SANS can increase heart rate. Many organs exhibit predominant tone (e.g., GI tract, bladder are more PANS whereas vascular tone, piloerector muscles, and sweat glands are only receive SANS).
