On Thu, 22 Mar 2001, Linda Walsh went:
> Do any of you know the mechanism by which caffeine causes
> vasoconstriction of blood vessels to the brain, while elsewhere it
> triggers vasodilation? I think the vasodilation may occur because
> methylxanthines like caffeine increase the release of nitric oxide,
> which in turn relaxes smooth muscle, but what's different in the
> CNS?
I don't know the answer, but I know where I'd start looking: I'd start
looking at the anatomical distribution of subtypes of adenosine
receptors (caffeine is an adenosine antagonist). For what it's worth,
here are factoids from the notes I took from several articles, circa
1997. Refs on request, but they're old anyway; I'm sure you could
find a more recent review.
A1 receptors
--are coupled to Gi and thus inhibit cAMP formation.
--caffeine has high affinity for them (as an antagonist).
--there's lots of 'em in hippocampus and neocortex.
--when activated, they can induce vasoconstriction (probably by
releasing angiotensin II or thromboxane) in renal and pulmonary
vasculature. (I'm not clear on what they do to cerebral
vasculature.)
--downregulate in response to activation by adenosine (their
endogenous ligand), but upregulate with chronic blockade by
caffeine.
A2A receptors
--are coupled to Gs and thus stimulate cAMP formation.
--caffeine has low affinity for them.
--when activated, they can induce vasodilation (probably by inducing
NO formation in endothelial cells) in cerebral vasculature.
A2B receptors
--are coupled to Gs and thus stimulate cAMP formation.
--when activated, can induce vasodilation (as in rat lung).
A3 receptors
--are coupled to Gi and thus inhibit cAMP formation.
--caffeine has low affinity for them.
--David Epstein
[EMAIL PROTECTED]
