The Contribution of cocoa additive to cigarette smoking addiction

RIVM report 650270002 Page 163 of 207
Octopamine
selective ß3-AR agonists but not with ß1-or ß2-agonists. Human adipocytes, which
endogenously express a high level of α2-ARs, exhibited a clear α2 -adrenergic
antilipolytic response to adrenaline but not to octopamine. In Syrian hamster
adipocytes, which also possess α2-ARs, octopamine induced only a weak
antilipolysis. Octopamine is a substrate of fat cell amine oxidases, with an apparent
affinity similar to that of noradrenaline. Thus, octopamine could be considered as an
endogenous selective ß3-AR agonist (11).
Octopamine stimulates adenylate cyclase. Via experimentation it was suggested that
octopamine acts on intestinal dopamine D1-receptor sites to produce relaxation of
rabbit jejunum through an increase of cAMP (cyclic adenosine monophosphate) (12).
Recently, a family of related mammalian 15 G protein-coupled receptors was
identified of which two members (TA1- and TA2-receptors) have been shown to
specifically bind and/or be activated by trace amines, such as phenylethylamine and
tryptamine. However, these receptors display low affinity for octopamine (13).
Pulmonary system
breathing frequency: no data available.
tidal volume: no data available.
lung compliance: no data available.
airway resistance: Noradrenaline is 6000 fold more potent than octopamine to
activate ß1-adrenergic receptors in guinea-pig atria and trachea. Octopamine had
no detectable activity in concentrations as high as 10 -4 M on the ß2-adrenoreceptor
of the isolated trachea. If octopamine is co-released with noradrenaline in
amounts proportional to their concentration, their activities at these structures are
too low to be physiologically significant (14).
Cardiovascular system
blood pressure: Effects of octopamine on sinus rate and atrial contractility were
investigated using the isolated atrium preparation of dog. When octopamine,
dopamine or noradrenaline was administered into the cannulated sinus node
artery, positive chronotropic and inotropic responses were dose-related. The DR50
values (dose ratio at 50% maximum response) of octopamine, dopamine and
noradrenaline were roughly 30-100: 30:1, respectively. The duration of action of
octopamine was longest. The positive chronotropic and inotropic responses to
octopamine are mainly due to tyramine-like action (15).
The perfusion of octopamine in pig produces an increase of cardiac output and
decreases the pulmonary vascular resistances. The changes in the lung circulation
are exerted by the direct action of this drug on nervous control of vascular walls
(octopamine dose is not mentioned in the abstract) (16).
Octopamine injected in lateral ventricle of conscious spontaneously hypertensive
rats decreased systolic blood pressure (SBP). The administration of pargyline, a
MAO inhibitor, which increased brain octopamine, resulted in a reduction of
systolic blood pressure. Octopamine hypotension was not antagonized by
selective antagonists of post-synaptic α-adrenoceptors, indicating that octopamine
may be involved in central blood pressure regulation (octopamine dose was not
mentioned in the abstract) (17). Experiments on rat mesenteric arterioles,
metarterioles and aortae demonstrate that octopamine is between 60 and 15,000
times less potent than noradrenaline on rat arterioles and metarterioles and is
incapable of eliciting more than 40% occlusion of these terminal vessels. It is
suggested that such data support the concept that octopamine, could serve as a