Adrenergic receptors

[Medic741]

Hey ya'all I have a question that I just can't find a good answer for in textbooks/FA/online and would love some help if anyone can explain this to me...

alpha-1 receptors = Gq and cause vasoconstriction, but as I'm finding the Gq stimulation of the smooth muscle endothelial lining (which alpha-1 stimulants would reach before hitting the sm muscle right?) causes NO synthesis, which diffuses and acts on the smooth muscle to relax associated vasculature. FA (pg 234, 2018) shows Gq stimulation causing vasoconstriction through Ca++ stimulating MLCK towards its active form & seems to ignore the endothelial effects of NO release in the vasculature...

I get that alpha-1 stim causes vasoconstriction, but can't reconcile this in my head and would love some guidance from someone who's wrapped their head around this one.

Thanks ya'all & hope everyone's having a good year!

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[ciucia53]

Sorry, maybe I'm really dumb - but where are you finding that Gq stimulation of endothelial cells causes NO synthesis?

 

[Medic741]

Sorry, maybe I'm really dumb - but where are you finding that Gq stimulation of endothelial cells causes NO synthesis?

Some class materials cited M3 receptor stimulation by bradykinin/Ach (M3=Gq) causes endothelial cells to produce NO. Pg 447 of FA has the best diagram of this. Basically the pathway is

Gq > increased Intracellular Ca++ stimulates NO Synthase (NOS) to convert L-Arg > NO which diffuses to the smooth muscle cell, activates guanyl cyclase causing GTP to be converted to cGMP in the smooth muscle cell. cGMP has the effect of then stimulating MLCK-phosphatase which causes smooth muscle relaxation

edit:
CV Physiology | Vascular Signal Transduction Mechanisms

 

[Medic741]

Answer looks like the M3 receptor is found on the vascular endothelium while the Alpha1 receptor is found directly on the smooth muscle... Ach stimulating M3 on the endothelium leads to NO production > diffusion > MLCK-phosphatase activation and relaxation while NE binding Alpha1 on vascular smooth muscle causes contraction... that's pretty neat.