NEUROENDOCRINOLOGY
LETTERS including Psychoneuroimmunology, Neuropsychopharmacology,
Reproductive Medicine, Chronobiology
and
Human Ethology
ISSN 0172–780X
An
Hormonal Role for Endogenous Opiate Alkaloids: Vascular Tissues
by George B. Stefano
(1,2), Wei Zhu (1), Patrick Cadet (1),
Kirk Mantione (1) and Thomas V. Bilfinger (1,2), Enrica Bianchi
(3) and Massimo Guarna (3)
1. Neuroscience Research Institute, State University of New
York/ College at Old Westbury, Old Westbury, New York, 11568
2.
Cardiothoracic Division, Department of Surgery, Health Sciences
Center, State University of New York at Stony Brook, Stony
Brook, New York, 11794. U.S.A.
3.
Department of Biomedical Sciences and Institute of Neurological
and Psychiatric Diseases, University of Siena, Italy
The
distribution of morphine-containing cells in the central nervous
system, adrenal gland, and its presence in blood may serve
to demonstrate that this signal molecule can act as a hormone
besides its role in cell-to-cell signaling within the brain.
This speculative review is the result of a literature evaluation
with an emphasis on studies from our laboratory. Opioid peptides
and opiate alkaloids have been found to influence cardiac
and vascular function. They have also been reported to promote
ischemic preconditioning protection in the heart. Given the
presence of morphine and the novel µ3 opiate receptor
on vascular endothelial cells, including cardiac and vascular
endothelial cells in the median eminence, it would appear
that endogenous opiate alkaloids are involved in modulating
cardiac function, possible at the hormonal level. This peripheral
target tissue, via nitric oxide coupling to µ opiate
receptors, may serve to down regulate the excitability of
this tissue given the heart's high performance state as compared
to that of the saphenous vein, a passive resistance conduit.
Taken together, morphine and other endogenous opiate alkaloids
may function as a hormone.
Introduction
Adrenal
Gland
Endogenous morphine has been identified in mammalian and invertebrate
neural tissues by various techniques, including gas-chromatography
mass spectrometry (GC/MS) [1-11]. Additionally, morphine has
been found to exist in the vertebrate adrenal gland by way
of immunocytochemistry and radioimmunoassay [1,12-19]. Recently,
we also found morphine present in the rat adrenal gland and
determined its identity by way of gas-chromatography mass
spectrometry (GC/MS) [20].
We have extended these studies to include the demonstration
of morphine in the rat adrenal medullary chromaffin PC-12
cell line by high performance liquid chromatography (HPLC)
coupled with electrochemical detection and GC/MS [20]. We
recently confirmed the presence of opiate alkaloids in this
cell line using nano electrospray ionization double quadrupole
orthogonal acceleration time of flight mass spectrometry (Q-TOF
MS)[21]. Also, in this report, the major morphine metabolite,
morphine 6-glucorinde (M6G) was identified. A single charge
ion with a mass of 462.17 da is also present in the PC12 extract
[21]. This value is identical to the calculated mass of M6G
and is identical to the mass obtained from the analysis of
authentic M6G [21].
We have recently reviewed the central nervous systems "morphinergic"
system [22]. Within this context and that which is noted for
the adrenal gland, morphine has the potential to be released
into the circulatory system, thus, making it a hormone. Morphine
is present in human and animal plasma, further suggesting
hormonal action [23-27]. Thus, we are left with the question
of what are the peripheral morphinergic targets. Based on
the work of our laboratory, we surmise that these targets
include, and are not limited to, immune and vascular tissues.
In the past we have discussed the role of endogenous morphine
in immune tissues [22,25,28-30]. In this review, we will examine
studies suggesting a vascular role for this new hormone.
