Autonomic Drugs: 2nd messenger systems Flashcards
What are the two types of cholinergic receptors (cholinoceptors)?aka ACh receptors
muscarinic and nicotinic
Nicotinic receptors are ligand gated channels, what does this mean?
activation causes a rapid increase in cellular permeability to Na and Ca, depolarization and excitation
What are the two types of nicotinic receptors?
Muscle type (Nm) Neuronal type (Nn)
Where are the nicotinic receptors found?
Nn: autonomic ganglia (ganglionic transmission) and adrenal medulla (secretion of catecholamines)
Nm: NMJ (neuromuscular transmission)
Muscarinic ACh receptors are G protein coupled receptors located on the plasma membrane of cells in the CNS, in organs innervated by what?
Parasympathetic nerves as well as on some tissues that are not innervated by these nerves aka endothelial cells
M1, what is the G class protein, location and effects?
q= increased IP3 and DAG and Increase Ca2+ locations = CNS = increased cognitive function Ganglia = depolarization
M2, what is the G class protein, location and effects?
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
M3, what is the G class protein, location and effects?
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)
Adrenergic receptors (Adrenoceptors) can be subdivided into alpha adrenoceptor and beta adrenceptor types. All adrenergic receptors belong to the family of what?
G protein linked receptors
First starting off with Beta receptors what is the potency series?
Isoproterenol, epi and then norepi
There are three subtypes of beta receptors B1, B2 and B3 what are their affinities for epi and norepi?
B1 and B3 receptors have approximately equal affinity for epi and norepinephrine
B2 receptors have higher affinity for epi than for norepinephrine
All beta adrenergic receptors stimulate adenylyl cyclase via interaction with Gs. This leads to what?
Activation of protein kinase A and altered function of numerous cellular proteins
Starting with B1, what is the g protein class, location and effect?
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
B2 what is the g protein class, location and effect?
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 )
B3, what is the g protein class, location and effect?
s = increased cAMP adipocytes = increased lipolysis (Activation of TAG lipase)
Moving on to the alpha adrenergic receptors, what is the potency series/
Epi , norepinephrine and isoproterernol
Alpha 1, what is the g protein class, location and effect?
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
Alpha 2, what is the g protein class, location and effect?
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
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?
S= increases cAMP
brain, effector tissues (ESp smooth muscle of the renal vascular bed) = relaxation of renal vascular smooth muscle
What is the g protein class, location and effect of D2?
i = decreased cAMP and decreased Ca2+ and increased K channels
brain, effector tissues, esp smooth muscle presynaptic nerve terminals = modulates transmitter release
Sensory carotid sinus baroreceptor fibers in the glossopharyngeal nerve have a major influence on what?
sympathetic outflow from the vasomotor center
What is the primary controlled variable in CV function?
mean arterial pressure
Changes in any variable that tend to alter mean arterial pressure evoke what?
Powerful homeostatic secondary responses that tend to compensate for the directly evoked changed
Finally lets review the receptors for the eyes. What affect does the alpha 1 receptor have?
Pupillary dilator (radial) muscle in the iris --contraction of the pupillary dilator causes mydriasis (dilation)
What affect does the Beta 2 receptor have?
Secretory epithelium of the ciliary body
–ciliary epithelium produces aqueous humor
What affect does M3 receptor have on the eye?
- Pupillary constrictor (Sphincter) muscle in the iris = contraction of the pupillary constrictor muscle causes miosis
- Ciliary Muscle = when the ciliary muscle contracts it adapts to short range focus, when it relaxes it adapts to long range focus
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?
Increased outflow reduces intraocular pressure useful for glaucoma
–all via a muscarinic drug
What is another therapy for glaucoma?
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.
