The β actions are mediated through cAMP (see Fig. 4.6). Adr activates membrane bound enzyme adenylyl cyclase through a regulatory protein Gs → ATP is broken down to cAMP at the inner face. This in turn phosphorylates a number of intracellular cAMPdependent protein kinases and initiates a series of reactions:
BIOCHEMICAL MEDIATION OF ADRENERGIC RESPONSES
β Actions
The β actions are mediated
through cAMP. Adr activates membrane bound enzyme
adenylyl cyclase through a regulatory protein Gs → ATP is broken down to cAMP at the inner face. This in turn phosphorylates a
number of intracellular cAMPdependent protein kinases and initiates a series of
reactions:
In liver and muscle, glycogen phosphorylase is
activated causing glycogenolysis while glycogen synthetase is inhibited. Both
actions result in hyperglycaemia and hyperlactacidemia. Neoglucogenesis in
liver adds to the response.
K+
is first released from liver → hyperkalaemia; followed by more prolonged
hypokalaemia due to K+ uptake in muscle and later in liver itself.
In adipose tissue, triglyceride lipase is activated → increased plasma free
fatty acids. Increased O2 consumption and heat production result primarily
by action on brown adipose tissue, which has predominant β3 receptors.
In heart,
proteins like troponin and phospholamban are phosphorylated. The former results
in increased interaction with Ca2+ at the myofilaments → increased force of
contraction; the latter causes sequestration of Ca2+ by sarcoplasmic reticulum → more rapid
relaxation. The activated protein Gs, in addition, interacts directly with the
Ca2+ channels in the membrane promoting influx of Ca2+ which reinforces the
positive inotropic action exerted through cAMP.
In the gut and bronchial muscle, relaxation (accompanied
with hyperpolarization) is induced, but the intermediate steps have not been
clearly delineated.
In pancreatic islets
activation of β2 receptors on α cells increases glucagon
secretion, and that on β cells increases insulin secretion, both by
raising intracellular cAMP. However, augmentation of insulin secretion is weak.
α Actions
The mediation of α actions is varied and
less well defined.
In
smooth muscles (including vascular)
that are contracted through α1 receptors, the
activated Gprotein increases IP3/DAG production → mobilization of Ca2+
from intracellular organelle → activation of calmodulin dependent myosin
light chain kinase → phosphorylation of myosin →contraction. The
vasoconstrictor α2 receptors probably
enhance Ca2+ influx without utilizing IP3.
The prejunctional
α2 receptor appears to
inhibit neuronal Ca2+ channels and also limit the intracellular availability of
Ca2+ by decreasing cAMP production. Transmitter (NA) release is consequently
diminished. Hyperpolarization through activation of K+ channels may also occur.
In the gut,
α2 receptor activation
hyperpolarizes the cholinergic neurone → decreased release of
ACh → reduced tone; whereas
α1 receptors located directly
on the smooth
muscle cell increase K+ efflux → hyperpolarization relaxation.
In pancreatic
β cells, stimulation of α2 receptors reduces the
formation of cAMP → decreased insulin release.
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