Autonomic Drugs: 2nd messenger systems

Question 1

What are the two types of cholinergic receptors (cholinoceptors)?aka ACh receptors

Answer 1

muscarinic and nicotinic

Question 2

Nicotinic receptors are ligand gated channels, what does this mean?

Answer 2

activation causes a rapid increase in cellular permeability to Na and Ca, depolarization and excitation

Question 3

What are the two types of nicotinic receptors?

Answer 3

Muscle type (Nm) 
Neuronal type (Nn)

Question 4

Where are the nicotinic receptors found?

Answer 4

Nn: autonomic ganglia (ganglionic transmission) and adrenal medulla (secretion of catecholamines)
Nm: NMJ (neuromuscular transmission)

Question 5

Muscarinic ACh receptors are G protein coupled receptors located on the plasma membrane of cells in the CNS, in organs innervated by what?

Answer 5

Parasympathetic nerves as well as on some tissues that are not innervated by these nerves aka endothelial cells

Question 6

M1, what is the G class protein, location and effects?

Answer 6

q= increased IP3 and DAG and Increase Ca2+ 
locations = CNS = increased cognitive function 
Ganglia = depolarization

Question 7

M2, what is the G class protein, location and effects?

Answer 7

i= inhibits adenylyl cyclase by opening K+ channels and closing Ca2+ channels; therefore decrease in cAMP
Locations = heart = cardiac inhibition (vagal inhibition that keeps the HR WNL)
Presynpatic nerve terminals = inhibition of acetylcholine and norepinephrine release

Question 8

M3, what is the G class protein, location and effects?

Answer 8

q = increased IP3 and DAG and Increased Ca2+
locations = smooth muscle = contraction (increased bladder contraction, bronchoconstriction and increased gut peristalsis)
vascular endothelium = vasodilation through activation of NO
Secretory glands = secretion (lacrimal, salivary and gastric acid)

Question 9

Adrenergic receptors (Adrenoceptors) can be subdivided into alpha adrenoceptor and beta adrenceptor types. All adrenergic receptors belong to the family of what?

Answer 9

G protein linked receptors

Question 10

First starting off with Beta receptors what is the potency series?

Answer 10

Isoproterenol, epi and then norepi

Question 11

There are three subtypes of beta receptors B1, B2 and B3 what are their affinities for epi and norepi?

Answer 11

B1 and B3 receptors have approximately equal affinity for epi and norepinephrine
B2 receptors have higher affinity for epi than for norepinephrine

Question 12

All beta adrenergic receptors stimulate adenylyl cyclase via interaction with Gs. This leads to what?

Answer 12

Activation of protein kinase A and altered function of numerous cellular proteins

Question 13

Starting with B1, what is the g protein class, location and effect?

Answer 13

s = increased cAMP and Ca2+
heart leads to positive inotropic and chrontropic responses = increased HR, Heart force, and AV nodal conduction velocity
JG cells stimulates renin secretion

Question 14

B2 what is the g protein class, location and effect?

Answer 14

s= increased cAMP 
smooth muscle (vascular, bronchial, GI and genitourinary) = relaxation (myosin light chain kinase is now in the inactive form) 
skeletal muscle = increased glycogenolysis and increased uptake of K 
Pancreatic islets ( b cells) = increased insulin secretion 
Pancreatic islets (alpha cells) = increased glucagon secretion 
Liver = increased glycogenolysis and increase gluconeogensis (via activation of hepatic glycogen phosphorylase causes inactivation of glycogen synthase )

Question 15

B3, what is the g protein class, location and effect?

Answer 15

s = increased cAMP 
adipocytes = increased lipolysis (Activation of TAG lipase)

Question 16

Moving on to the alpha adrenergic receptors, what is the potency series/

Answer 16

Epi , norepinephrine and isoproterernol

Question 17

Alpha 1, what is the g protein class, location and effect?

Answer 17

q= increased IP3 and DAG and increased Ca2+
vascular smooth muscle = contraction
genitourinary smooth muscle = contraction
intestinal smooth muscle = relaxation
liver = increased glycogenolysis and increased gluconeogensis

Question 18

Alpha 2, what is the g protein class, location and effect?

Answer 18

i = decreased cAMP and decreased Ca2+ channels and increased K channels
presynpatic nerve terminals = inhibition of norepinephrine and acetylcholine release
platelets = aggregation
adipocytes = inhibition of lipolysis
pancreatic islets = decreased insulin secretion

Question 19

Dopamine receptors are the next type of g protein linked 2nd messengers. D1/D5 and D2 both act on adenylyl cyclase and cAMP. what is the g protein class, location and effect of D1/D5?

Answer 19

S= increases cAMP

brain, effector tissues (ESp smooth muscle of the renal vascular bed) = relaxation of renal vascular smooth muscle

Question 20

What is the g protein class, location and effect of D2?

Answer 20

i = decreased cAMP and decreased Ca2+ and increased K channels
brain, effector tissues, esp smooth muscle presynaptic nerve terminals = modulates transmitter release

Question 21

Sensory carotid sinus baroreceptor fibers in the glossopharyngeal nerve have a major influence on what?

Answer 21

sympathetic outflow from the vasomotor center

Question 22

What is the primary controlled variable in CV function?

Answer 22

mean arterial pressure

Question 23

Changes in any variable that tend to alter mean arterial pressure evoke what?

Answer 23

Powerful homeostatic secondary responses that tend to compensate for the directly evoked changed

Question 24

Finally lets review the receptors for the eyes. What affect does the alpha 1 receptor have?

Answer 24

Pupillary dilator (radial) muscle in the iris 
--contraction of the pupillary dilator causes mydriasis (dilation)

Question 25

What affect does the Beta 2 receptor have?

Answer 25

Secretory epithelium of the ciliary body

–ciliary epithelium produces aqueous humor

Question 26

What affect does M3 receptor have on the eye?

Answer 26

1. Pupillary constrictor (Sphincter) muscle in the iris = contraction of the pupillary constrictor muscle causes miosis
2. Ciliary Muscle = when the ciliary muscle contracts it adapts to short range focus, when it relaxes it adapts to long range focus

Question 27

Ciliary muscle contraction (M3) puts tension on the trabecular meshwork, opening its pores and facilitating outflow of the aqueous humour into the canal of schlemm. What is this useful for?

Answer 27

Increased outflow reduces intraocular pressure useful for glaucoma
–all via a muscarinic drug

Question 28

What is another therapy for glaucoma?

Answer 28

B2 adrenoceptors in the ciliary epithelium facilitate the secretion of aqueous humour.
–therefore blocking B2 adrenoceptors with beta blockers reduces secretory activity and reduces intraocular pressure providing another therapy for glaucoma.