Questions on pharmacology GPCR related

seraphimvc

hey guys,wonder any of you can help me out,sent an email to my lecturer but no reply ,maybe he is away from country at the moment.thank you in advance!:)

is a part of my practical report ,

This is so far what i written down :
A free G-protein consists of 3 subunits with a GDP :GDP occupies the
binding site on the α subunit , separately , β and γ subunits bind
together form a βγ complex .Different subtypes of all three subunits
determine different target to activate .

Examples of GPCR including H1 receptor and muscarinic receptor which are
the main target receptors we used to determine the drug dose and response.

Phospholipase C Pathway:
When an agonist activate GPCR with α subunit subtype class Gq ,it
upregulate Phospholipase C to produce effect of increasing the
production of Inositol trisphosphate(IP3) and diacylglycerol (DAG) . IP3
releasing Ca2+ from intracellular storage. DAG activates protein kinase
C by the increased calcium ions from IP3 .
H1 receptor is an example of receptor involved in this pathway.
Histamine is the agonist of H1 receptor ,increasing of IP3 will cause
the contraction of smooth muscles, e.g. ileum muscle .

Adenylyl Cyclase Pathway :
When an agonist activate GPCR with α subunit subtype class Gs ,it will
produce effect of increasing the catalytic activity response of adenylyl
cyclase (AC) ,thus raising the concentration of cAMP ,activating protein
kinase A .
Muscarinic receptor is an example of receptor involved in this pathway.
Acetylcholine is the agonist of muscarinic acetylcholine receptor
,stimulating muscle contraction

here is what i am confused:
1.acetylcholine is activating muscarinic receptor,that receptor has
something to do with AC pathway,but from the information i have been
looking around,seems doesnt make sense to me:the increasing of cAMP
production in smooth muscle causes smooth muscle relaxation!(pg 37,Rang
& dale's,Edition 6th)which means if AC pathway activated,we should get
the opposite effect.
2.from the page,http://en.wikipedia.org/wiki/Adrenergic_receptor,in the
comparison table,these adrenoreceptor seems have some very similiar
fucntion of causing relaxing and contraction of smooth muscle as
well.but they said,smooth muscle contraction:Gi: adenylate cyclase
inactivated, cAMP down.i assume that there is a different subunit Gi
involved,so that's fine for me(or it is that case?),but this time seems
contraction of smooth muscle need the inactivate of AC pathway?even
different drug or receptor,but i guess they will take the same method to
achieve something,but seems the function of AC pathway is confusing here.

hoep anyone can help me,would be very appreciated.

2Scoops

Ach stimulation of muscarinic receptors will inhibit adenylate cyclase activity, not increase it. Everything else looks right.

seraphimvc

2Scoops wrote: »

Ach stimulation of muscarinic receptors will inhibit adenylate cyclase activity, not increase it. Everything else looks right.

ah,very appreciated your reply:D just wanna make it sure again:
so,is that mean ,ACh inhibiting the AC pathway,causing smooth muscle contraction?and we actually call ACh the agonist merely for it activating the muscarinic receptor,*but it actually decreasing cAMP ,inhibit AC pathway.

so this should work 'formally':
Adenylyl Cyclase Pathway :
When a drug activate GPCR with α subunit subtype class Gs ,it will produce effect of increasing the catalytic activity response of adenylyl cyclase (AC) ,thus raising the concentration of cAMP ,activating protein kinase A ,and relaxing the smooth muscles.
Muscarinic receptor is an example of receptor involved in this pathway. Acetylcholine is the agonist of muscarinic acetylcholine receptor ,decreasing the production of cAMP, inhibiting the AC pathway and thus stimulating muscle contraction ,e.g. ileum muscle

the agonist to activate the AC pathway and agonist for muscarinic receptor so that it will inhibit AC pathway,they confused me,yea?:)

2Scoops

The inhibition of the AC pathway per se is not responsible for contraction - only inhibiting relaxation. Activation of the muscarinic receptors by Ach increases intracellular Ca2+ which causes contraction. Maybe just pick a different example of a receptor involved with the AC pathway?

seraphimvc

sorted,the report was due on friday:)

say in simpler way:
seems appear that muscarinic receptors have 2 types in smooth muscle:M2 and M3,m2 preventing relaxation(block AC pathway)while M3 (causing contraction)is dominating in intestinal muscle.that's what i was confused:Dsorted!