Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.1 (NADPH-diaphorase)
 3,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular mechanism of nitric oxide synthase (NOS)-containing nerve regeneration is still unknown. It is believed that growth factors are involved in this phenomenon. We investigated the change of NOS containing nerve fibers and the mRNA expression of insulin like growth factor (IGF)-I, nerve growth factor (NGF), transforming growth factor (TGF)-alpha, TGF-beta1, TGF-beta2, TGF-beta3, vascular endothelial growth factor (VEGF), endothelial NOS (eNOS) and neuronal NOS (nNOS) on the penis after cavernous nerve neurotomy in rats. Male rats were divided into four groups: (1) sham operation (n = 14); (2) unilateral neurotomy of a 5 mm segment of the cavernous nerve (n = 21); (3) unilateral neurotomy with growth hormone (n = 14); and (4) bilateral neurotomy (n = 21). Electrostimulation of the intact cavernous nerve or pelvic ganglion were performed at one, three and six months. Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining and immunohistochemistry were used to identify NOS in the penis. The gene expression for growth factors, eNOS and nNOS were investigated in corporal tissue by reverse transcriptase-polymerase chain reaction (RT-PCR). One month after neurotomy, both unilateral and bilateral neurotomy groups showed significant decreases in NOS-containing nerve fibers on the dorsal and intracavernosal nerves on the side of neurotomy. Significantly lower mRNA expression of nNOS, IGF-I and TGF-beta2, higher mRNA expression of eNOS and VEGF189 were shown in these groups. At three months, the number of NOS-containing nerve fibers in the unilateral neurotomy group increased only slightly, while the GH-treated group showed a significant increase. At six months, those in the intracavernosal nerve only increased in a significant amount (P < 0.0001), however mRNA expression of nNOS, IGF-I and TGF-beta2 showed a significant increase as early as at three months. After bilateral neurotomy, the NOS-positive nerve fibers in the dorsal and intracavernosal nerve were significantly decreased at one month and remained so at six months; no erectile response could be elicited by pelvic ganglion stimulation. In the unilateral neurotomy group at six months, more NOS-positive neurons in the pelvic ganglia were found on the intact side than on the side of the neurotomy (P < 0.003), indicating that the regeneration derived from pelvic ganglion neurons on the intact side. Furthermore, electrostimulation in the unilateral neurotomy group revealed a greater maximal intracavernosal pressure and a shorter latency period at six months than at one month (P < 0.014, P < 0.001, respectively). These data suggest that IGF-I and TGF-beta2 may play a key role in the regeneration of nNOS-containing nerve fibers in the dorsal and intracavernosal nerves, and eNOS increases temporarily in the intracavernous involving VEGF189 after unilateral cavernous nerve injury.
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PMID:IGF-I and TGF-beta2 have a key role on regeneration of nitric oxide synthase (NOS)-containing nerves after cavernous neurotomy in rats. 1055 3

Ghrelin is a potent stimulant for growth hormone (GH) secretion and feeding. Recent studies further show a critical role of ghrelin in the regulation of sleep-wakefulness. Pedunculopontine tegmental nucleus (PPT), which regulates waking and rapid eye movement (REM) sleep, expresses GH secretagogue receptors (GHS-Rs). Thus, the present study was carried out to examine electrophysiological effects of ghrelin on PPT neurons using rat brainstem slices, and to determine the ionic mechanism involved. Whole cell recording revealed that ghrelin depolarizes PPT neurons dose-dependently in normal artificial cerebrospinal fluid (ACSF). The depolarization persisted in tetrodotoxin-containing ACSF, although action potentials did not occur. Application of [d-Lys(3)]-GHRP-6, a selective antagonist for GHS-Rs, almost blocked the ghrelin-induced depolarization. Furthermore, the ghrelin-induced depolarization was reduced in high K(+) ACSF or low Na(+) ACSF, and abolished in high K(+)-low Na(+) ACSF or in a combination of low Na(+) ACSF and recordings with Cs(+)-containing pipettes. An inhibitor of Na(+)/Ca(2+) exchanger had no effect on the depolarization. Most of the PPT neurons recorded were characterized by an A-current or both the A-current and a low threshold Ca(2+) spike, and they were predominantly cholinergic as revealed by nicotinamide adenine dinucleotide phosphate-diaphorase staining. These results suggest that ghrelin depolarizes PPT neurons postsynaptically and dose-dependently via GHS-Rs, and that the ionic mechanisms underlying the ghrelin-induced depolarization include a decrease of K(+) conductance and an increase of non-selective cationic conductance. The results also support the notion that ghrelin plays a role in the regulation of sleep-wakefulness.
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PMID:Electrophysiological effects of ghrelin on pedunculopontine tegmental neurons in rats: An in vitro study. 1911 91