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Preliminary Investigation On Effects Of Burantashi Extract On Liver Enzymes Of Aibino Male And Female Whistar Rats
CHAPTER ONE -- [Total Page(s) 3]
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In primates, including humans the L-arginine nitric oxide guanylyl
cyclase cyclic guanosine monophosphate (cGMP) pathway is the key
mechanism of penile erection. Nitric oxide is produced from oxygen and
L-arginine under the control of nitric oxide synthase (NOS). Sexual
arousal stimulates neural pathways that result in the release of NO from
nerves and endothelial cells directly into the penis. NO penetrates
into the cytoplasm of smooth muscle cells
and binds to guanylyl
cyclase. The interaction of NO with guanylyl cyclase causes a
conformational change in the enzyme, which results in the catalytic
production of 3,5 cyclic guanosine monophosphate from guanosine
5’triphosphate. Cyclic cGMP activities cGMP dependent protein kinase
(PKG) which in turn phosphorylates several proteins. These protein
kinase interactions results in reduced intraocular calcium levels and a
consequent relaxation of arterial and trabecular smooth muscle leading
to arterial dilation. Venous constriction and the rigidity of penile
erection.
Since cGMP plays a key role in this process, potential
interventions for inadequate smooth muscle relaxation include increasing
the level of intracellular cGMP. PDE-5 normally inhibits penile
erection by degrading cGMP. This degradation occurs at the catalytic
site in the presence of bound zinc. PDE-5 inhibitors lower the activity
of PDE-5 by competing with cGMP and consequently raise the level of
cGMP. In the absence of stimulation of the NO pathway. PDE-5 inhibition
is ineffective in isolated strips of corpus c avernosum, sildenafil
relaxes the smooth muscle by amplifying the effects of the normal,
endogenous cGMP- dependent relaxation mechanisms but produces little
effect in the absence of a NO donor. Since sexual arousal stimulates
this pathway specifically in the penis, PDE-5 inhibitor has a relatively
small effect on smooth muscle in other tissues.
PDE-5 is the
predominant phosphodiesterase in the corpus carvernosum, however, at
least 11 families of PDE have been identified in mammals, some PDE types
are associated with more than one gene and some mRNA exhibit two or
more splice variants. The result is more than 50 species of PDE. Some
types of PDE are specific for either cyclic adenosine monophosphate
(cGMP) or cGMP, and some degrade both PDE, for example degrades both
cGMP and cGMP. Whereas PDE-4 is specific for Camp-5 and PDE-5 is
specific for cGMP. The cross reactivity of PDE inhibitors can be
attributed largely to similarities of their homologous catalytic domain.
Messager RNA has been detected in human corpus cavernosum tissue for
the human PDE isoforms-PDE-1A, PDE-1B, PDE-1C, PDE-2A, PDE-3A, PDE-4A,
PDE-4B, PDE-4C, PDE-4D, PDE-5A, PDE-7A, PDE-8A, and PDE-9A. Most
mammalian PDEs are dimers but the functional significance of this
dimerization is unknown, some like PDE5, have two identical submits
(homodimers) and some like PDE-6 have two different submits
(heterodimers).
The PDE-5 also differs in the nature of the
regulatory domain of the enzyme and in the role of phosphorylation. In
all cases, the catalytic domain is located towards the carboxylterminus
and the regulatory domain is located towards the amino terminus. A PDE-5
monomeric fragment retains the essential catalytic features of the
domain full length enzyme.
NITRIC OXIDE REGULATION OF PENILE ERECTION
Biology And Therapeutic Implications
For
approximately a decade now, substantial evidence has accrued supporting
nitric oxide (NO) as the central component of major signal transduction
system that ats in the penis to mediate the erectile response. This
molecules subserve a
Unique biochemical cascade invading production
of the potent second messenger molecule, 3’5’ cyclic guanosine
monophosphate (cGMP) and its activation of protein kinase G (PKG) which
induces physiologic penile erection by regulating the state of penile
smooth muscle contractility (Burnett, 1997). In fact, current data
support the notion that this NO based biochemical cascade represent a
convergence of cellular biochemical and molecular inputs, which on the
signal transduction regulatory level, is indispensable for the mechanism
of penile erection (Hedland et al., 2000). Consistent with the
importance of NO radiation of penile erection, its biology in the penis
is quite complex, involving multiple regulatory interactions, the
molecule itself may target several biochemical mechanisms that achieve
erectile tissue relaxation but is also the target of a host of
modulatory influences that determines its release and mode of action in
erectile tissue. At the same time, premier signal transduction mechanism
has been exploited for therapeutic purposes, specifically in the
clinical management of erectile dysfunction. Discoveries pertaining to
the field of NO biology in the penis have, in recent years been rapidly
translated into the clinical management of the first orally effective
pharmacotherapy for erectile dysfunction, sildenafil citrate (Viagra)
(Goldstein et al., 1998).
NO BIOLOGY IN THE PENIS
Traditional
understanding of the action of NO in the penis invokes the constitutive
formation of this molecule under normal physiologic conditions with the
expression and activities of the enzyme, sources localized to neural and
endothelial components of the corporal tissue. The verification that NO
derives from the autonomic innervations supplying the penis has
directly supported the description of this molecule as a peripheral
neurotransmitter of non adrenergic, no cholinergic-1992 mediated penile
erection (Kim et al.,1991) the confirmation that the molecule also is
produced within vascular and trabecular endothelium comprising the
penile vascular supply, has offered additional support for the role of
NO serving as an endothelial relaxation factor of penile erection
(kimoto et al., 1990, knispel et al., 1991, azadzoic et al., 1992,
Hedlund et al., 2000).
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ABSRACT - [ Total Page(s): 1 ]This work was carried out to investigate the effects of Burantashi extract on liver enzymes of albino male and female whistar rats. Burantashi is a popular seasoning agent to barbecued meat (suya) in Nigeria,mostly found in the northern part of the Nigeria. Liver Enzymes are those enzymes that plays important role in the liver both in function and regulation. Erectile dysfunction (ED) is defined as the consistent or recurrent inability of a man to attain or maintain penile erection, sufficient f ... Continue reading---
