UNIPROT:Q07644 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:Q07644 (polypeptide)
72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enzyme histochemistry, in combination with immunohistochemistry was used to establish the neurochemistry of neurons in the vas deferens and pelvic ganglia of the guinea-pig. Nerve fibres characterised by reactivity for reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase reactivity formed a dense network in the lamina propria and circular muscle layer of the vas deferens, but were very sparse in the longitudinal muscle layer of the vas deferens. NADPH-diaphorase reactivity was also present in nerve fibres forming a dense perivascular plexus in many of the arteries in the pelvic region and in some of the endothelial cells, especially near the origin of the capillaries. Nerves with vasoactive intestinal polypeptide (VIP)-immunoreactivity had a similar distribution to NADPH-diaphorase reactive nerves. Tyrosine hydroxylase (TH)-immunoreactive nerve fibres were found in both muscle layers of the vas deferens. There was no coexistence of VIP- and TH-immunoreactivities in nerve fibres in the vas deferens. In the anterior pelvic ganglia, the origin of the nerve fibres in the vas deferens, several classes of neurons could be identified by the presence or absence of the reactivity for NADPH-diaphorase and immunoreactivity for VIP and TH. Neurons containing both VIP and NADPH-diaphorase reactivity accounted for 40% of neurons in the ganglia. Neurons with VIP-immunoreactivity but not NADPH-diaphorase reactivity accounted for 6%. TH-immunoreactive neurons accounted for 22% of neurons in the anterior pelvic ganglia. Very rare cells (< 1%) contained both VIP- and TH-immunoreactivities. The remaining neurons, which were not labelled by any of these markers, comprised 31% of neurons in anterior pelvic ganglia. These results demonstrate the existence of NADPH-diaphorase reactivity in neurons containing VIP-immunoreactivity, thus suggest that nitric oxide may be a neurotransmitter in guinea-pig vas deferens, especially in the circular muscle layer, in the arteries, and in other pelvic organs innervated by pelvic ganglia.
...
PMID:NADPH-diaphorase and other neuronal markers in nerves and ganglia supplying the guinea-pig vas deferens. 791 4

The immunocytochemical distribution and messenger RNA expression of the prohormone convertases PC1 and PC2 involved in the posttranslational processing of precursor proteins were analyzed in mouse and rat pancreatic islets. Immunocytochemical colocalization studies demonstrated a close association of insulin with both PC1 and PC2 in the adult mouse and rat pancreas. The coexpression of insulin with the prohormone convertases was further examined in rat pancreatic tumors induced by streptozotocin-nicotinamide treatment. These insulin-synthesizing tumors expressed PC1 and PC2, whereas insulin-silent adenomas did not. Colocalization studies demonstrated that only PC2, not PC1, colocalizes with glucagon, pancreatic polypeptide, and somatostatin. The highest levels of PC2-like immunoreactivity were observed in the glucagon-containing alpha-cells. Ontogeny studies carried out by in situ hybridization in mice showed the first detectable expression of the prohormone convertases in the pancreatic primordium at midgestation, starting for PC1 on embryonic day 11 and for PC2 on embryonic day 10. Enzyme expression was further confirmed by immunocytochemistry, which detected the presence of immunoreactive PC1- and PC2-like proteins on embryonic days 14 and 17, respectively. Taken together, our data suggest that both PC1 and PC2 play a role in proinsulin processing in vivo, whereas PC2 is a likely candidate convertase participating in the processing of proglucagon, propancreatic polypeptide, and prosomatostatin in pancreatic islets.
...
PMID:Developmental expression of the prohormone convertases PC1 and PC2 in mouse pancreatic islets. 792 29

In cat middle cerebral arterial strips denuded of the endothelium, nicotine produced a relaxation that was abolished by treatment with hexamethonium. The relaxation was partially inhibited by treatment with NG-nitro-L-arginine (L-NNA), a nitric oxide (NO) synthase inhibitor, and oxyhemoglobin, an NO scavenger. The remaining relaxation in the media containing L-NNA was abolished in the strips made unresponsive to calcitonin gene-related peptide (CGRP) by its repeated application. However, this was not the case when the strips were made tachyphylaxic to vasoactive intestinal polypeptide. The nicotine-induced relaxation was also partially attenuated by pretreatment with capsaicin; the remaining relaxation was abolished by L-NNA but not by its D-enantiomer. The inhibitory effect of L-NNA was reversed by L- but not D-arginine. Histochemical study revealed that injections of ethanol into the vicinity of pterygopalatine ganglion abolished the positive staining for nicotinamide adenine dinucleotide phosphate diaphorase activity and the CGRP immunoreactivity in perivascular nerves innervating the middle cerebral artery of the ipsilateral side. The nicotine-induced relaxation in the middle cerebral artery from the ethanol-injected side was markedly inhibited compared with that from the nontreated side, whereas the relaxations induced by exogenously applied NO and CGRP were unaffected. We conclude that nicotine stimulates nicotinic receptors in nerve terminals and liberates NO or NO-like substance(s) and CGRP as neurotransmitters in cat middle cerebral arteries.
...
PMID:Neurogenic relaxations caused by nicotine in isolated cat middle cerebral arteries. 807 71

The overexpression and purification of recombinant rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase (3 alpha-HSD; EC 1.1.1.50) in Escherichia coli are described. The properties of the homogeneous recombinant 3 alpha-HSD (r3 alpha-HSD) confirm that a single polypeptide can function as a HSD, as a dihydrodiol dehydrogenase, and as an aromatic aldehyde, ketone, and quinone reductase. Cys-170, Cys-242, and Cys-217, implicated by bromoacetoxysteroid affinity-labeling agents as points of contact for the C-3, C-11, and C-17 positions of steroid ligands, were mutated to alanines. Unexpectedly, the homogeneous C170A and C242A mutants were kinetically similar to wild-type r3 alpha-HSD. By contrast, the C217A mutant gave Km values that were 4-fold higher for androstanedione and 2-fold higher for NADH. Inspection of the recently solved crystal structure of rat liver 3 alpha-HSD (Hoog, S. S., Pawlowski, J. E., Alzari, P. M., Penning, T. M., and Lewis, M. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 2517-2521) places Cys-170 and Cys-242 on the periphery of an alpha/beta-barrel so that they cannot be involved in catalysis of steroid recognition. This demonstrates that bromoacetoxysteroid affinity-labeling agents may provide misleading information regarding the topography of steroid hormone binding sites. When NADPH was modeled into the crystal structure of 3 alpha-HSD, Tyr-55 was implicated as the general acid, since it is in close proximity to the C-4 position of the nicotinamide ring and could polarize the substrate carbonyl. In support of this model, the purified Y55F mutant was found to be catalytically inactive, but still formed an E-NADPH complex (measured by fluorescence titration) and an E-NADH-testosterone complex (measured by equilibrium dialysis). The ability of the Y55F mutant to form binary and ternary complexes, but not aid in hydride transfer, is consistent with Tyr-55 acting as the general acid. 3 alpha-HSD is a member of the aldo-keto reductase superfamily, and Tyr-55 is invariant in members of this family where it may perform a similar function. Tyr-205 is present in a pentapeptide sequence that is conserved in HSDs that belong to the short-chain alcohol dehydrogenase family and has been implicated as the general acid within these enzymes. The Y205F mutant was found to be kinetically similar to wild-type r3 alpha-HSD.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Overexpression and mutagenesis of the cDNA for rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase. Role of cysteines and tyrosines in catalysis. 817 84

Nitric oxide (NO) plays an important physiological role in regulating gastrointestinal motility. Involvement of endogenous NO was evaluated in the response to non-adrenergic, non-cholinergic (NANC) nerve stimulation of the dog sphincter muscle of Oddi. Transmural electrical stimulation (TES), nicotine (10(-5) M) and K+ (10 mM) produced only a relaxation in the sphincter muscle strips contracted with substance P, which was not potentiated by atropine. The TES-induced relaxation was abolished by tetrodotoxin (3 x 10(-7) M) and oxyhaemoglobin (1.6 x 10(-5) M), but not affected by atropine (10(-7) M), propranolol (10(-7) M), phentolamine (10(-7) M), indomethacin (10(-6) M), cholecystokinin (CCK, 10(-8) M) and vasoactive intestinal polypeptide (VIP, 10(-8) M). The relaxation was also abolished by treatment with NG-nitro-L-arginine (L-NA, 10(-5) M), an NO synthase inhibitor. Nicotine produced a transient relaxation, which was abolished by tetrodotoxin, hexamethonium (10(-5) M) and L-NA, but not affected by atropine and NG-nitro-D-arginine (D-NA, 10(-5) M). The addition of K+ elicited a transient relaxation, which was abolished by tetrodotoxin and L-NA. The inhibitory effects of L-NA were antagonized by L-arginine (10(-3) M). The presence of neurons containing nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase was histochemically demonstrated in the sphincter of Oddi. These findings may indicate that TES, nicotine and K+ liberate NO from NANC inhibitory nerve which is involved in the relaxation of the dog sphincter of Oddi. The muscular tone does not seem to be regulated by cholinergic nerves under the experimental conditions used.
...
PMID:Functional role and histological demonstration of nitric-oxide-mediated inhibitory nerves in dog sphincter of Oddi. 857 10

Transhydrogenase catalyzes the reduction of NADP+ by NADH coupled to the translocation of protons across a membrane. The polypeptide composition of the enzyme in Rhodospirillum rubrum is unique in that the NAD(H)-binding domain (called Ths) exists as a separate polypeptide. Ths was expressed in Escherichia coli and purified. The binding of nucleotide substrates and analogues to Ths was examined by one-dimensional proton nuclear magnetic resonance (NMR) spectroscopy and by measuring the quenching of fluorescence of its lone Trp residue. NADH and reduced acetylpyridine adenine dinucleotide bound tightly to Ths, whereas NAD+, oxidized acetylpyridine adenine dinucleotide, deamino-NADH, 5'-AMP and adenosine bound less tightly. Reduced nicotinamide mononucleotide, NADPH and 2'-AMP bound only very weakly to Ths. The difference in the binding affinity between NADH and NAD+ indicates that there may be an energy requirement for the transfer of reducing equivalents into this site in the complete enzyme under physiological conditions. Earlier results had revealed a mobile loop at the surface of Ths (Diggle, C., Cotton, N. P. J., Grimley, R. L., Quirk, P. G., Thomas, C. M., and Jackson, J. B. (1995) Eur. J. Biochem. 232, 315-326); the loop loses mobility when Ths binds nucleotide; the reaction involves two steps. This was more clearly evident, even for tight-binding nucleotides, when experiments were carried out at higher temperatures (37 degrees C), where the resonances of the mobile loop were substantially narrower. The binding of adenosine was sufficient to initiate loop closure; the presence of a reduced nicotinamide moiety in the dinucleotide apparently serves to tighten the binding. Two-dimensional 1H NMR spectroscopy of the Ths-5'-AMP complex revealed nuclear Overhauser effect interactions between protons of amino acid residues in the mobile loop (including those in a Tyr residue) and the nucleotide. This suggests that, in the complex, the loop has closed down to within 0.5 nm of the nucleotide.
...
PMID:Interaction of nucleotides with the NAD(H)-binding domain of the proton-translocating transhydrogenase of Rhodospirillum rubrum. 862 68

The rat uterus is innervated by sensory and autonomic nerves. Sensory and sympathetic fibers travel in the hypogastric nerves and are associated with the thoracolumbar spinal cord levels T13-L3. The inferior mesenteric ganglion (IMG) contains the somata of sympathetic postganglionic neurons and some of these may project axons to the uterus. Sensory and parasympathetic fibers travel in the pelvic nerve and are associated with the lumbosacral cord levels L6-S1 and pelvic ganglion (PG). We previously reported data concerning the neurochemical anatomy of the PG with regard to the uterine innervation; the present study was undertaken to characterize the neurochemical anatomy of the IMG with regard to it involvement in uterine innervation. A retrograde axonal tracer was used to verify projections of axons of IMG neurons to the uterus. Immunostaining of cryostat sections of the IMG revealed neurons immunoreactive for neuropeptide Y (NPY) and for tyrosine hydroxylase (TH). Immunostaining for the synaptic terminal protein synapsin I (SYN) revealed numerous fine terminals immediately surrounding the principal neurons and in the interneuronal spaces. Varicosities immunoreactive for calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), enkephalin (ENK), substance P (SP) and galanin (GAL) appear to be associated with principal neurons. Additional varicosities stained for nicotinamide adenine dinucleotide phosphate (reduced)-diaphorase (NADPH-d) and nitric oxide synthase (NOS), thus indicating sites of neuronal nitric oxide synthesis. This study revealed that the IMG contains uterine-related neurons and that some of the retrogradely labeled uterine-related neurons contain NPY, TH or both NPY/TH. In addition, uterine-related neurons received abundant afferent inputs indicated by SYN-immunoreactive (-ir) terminals and some of these varicosities labeled for GAL, CGRP, VIP, ENK, or NADPH-d/NOS.
...
PMID:Identification of uterine-related sympathetic neurons in the rat inferior mesenteric ganglion: neurotransmitter content and afferent input. 881 65

Combined nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry, nitric oxide synthase (NOS) and vasoactive intestinal polypeptide (VIP) immunocytochemistry were used to study the distribution of NOS- and VIP-containing nerve elements in the feline pylorus. A large number of stained multipolar neurons was found in the myenteric plexus. However, some NADPH-d and NOS positive neurons were also observed in the submucous plexus and in the internal part of muscular layer. A few stained perikarya were found in the tunica mucosa, in a very close situation to the blood vessels. A large number of thin varicose fibres, with intense reaction for all markers were seen around or in close contact with the unstained perikarya to the blood vessels and some of them around the pyloric glands. The density of NOS and NADPH-d positive nerve elements was much higher than that of VIP-immunoreactive (IR) nerve elements. Our results suggest that nitric oxide (NO) might act as a regulatory neurotransmitter of the pyloric sphincter, blood flow and secretion in this region.
...
PMID:Nitric oxide synthase-containing nerve elements in the pylorus of the cat. 884 6

Short axon (SA) cells in the olfactory bulb are subdivided into six types after Golgi impregnation, although their functional significance is not fully elucidated. In the present study, we examined the golden hamster olfactory bulb by immunohistochemistry to localize neurotransmitters, neuron-specific marker, and nitric oxide synthase (NOS) in the SA cells. Enzyme histochemical staining was also performed to detect the activity of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase, which is identified with NOS. In the main olfactory bulb (MOB), neuropeptide Y (NPY)-, NOS-, and NADPH-diaphorase-positive SA cells were detected in the glomerular layer (GL), vasoactive intestinal polypeptide (VIP)-positive SA cells in the external plexiform layer (EPL), and NPY-, somatostatin (SOM)-, protein gene product 9.5 (PGP 9.5)-, NOS-, and NADPH-diaphorase-positive SA cells in the granule cell layer (GCL). In the accessory olfactory bulb (AOB), VIP- and PGP 9.5-positive SA cells were detected in the mitral/tufted cell layer (MTL), and NPY-, SOM-, NOS-, and NADPH-diaphorase-positive SA cells in the GCL. The common presence of NPY- SOM-, VIP-, PGP 9.5-, NOS-, and NADPH-diaphorase-positive SA cells in both the MOB and the AOB may suggest that respective types of cells with the same immunoreactivity play the same role no matter where these cells are located in the MOB or the AOB.
...
PMID:Immunohistochemical and enzyme histochemical characteristics of short axon cells in the olfactory bulb of the golden hamster. 889 91

Cyclic ADP ribose (cADPR) is a potent Ca(2+)-releasing agent, and putative second messenger, the endogenous levels of which are tightly regulated by synthetic (ADP-ribosyl cyclases) and degradative (cADPR hydrolase) enzymes. These enzymes have been characterized in a number of mammalian and invertebrate tissues and their activities are often found on a single polypeptide. beta-NAD+, cGMP and nitric oxide (NO) have been reported to mobilize Ca2+ in the sea urchin egg via the cADPR-mediated pathway. We now report that in sea urchin egg homogenates, nicotinamide inhibits the Ca(2+)-mobilizing action of beta-NAD+, cGMP and NO, but has no effect on cADPR-induced Ca2+ release. Moreover, nicotinamide inhibits cGMP-induced regenerative Ca2+ waves in the intact sea urchin egg. By successfully separating the cADPR-metabolizing machinery from that which releases Ca2+, we have shown that nicotinamide inhibits cADPR-mediated Ca2+ signalling at the level of cADPR generation. Importantly, nicotinamide had no effect upon the hydrolysis of cADPR, and its selective action on cyclase activity was supported by its inhibition of purified Aplysia ADP-ribosyl cyclase, which does not exhibit detectable hydrolytic activity. The action of nicotinamide in blocking Ca2+ release by beta-NAD+, cGMP and NO strongly suggests that these agents act as modulators of cADPR synthesis rather than to sensitize calcium release channels to cADPR.
...
PMID:Nicotinamide inhibits cyclic ADP-ribose-mediated calcium signalling in sea urchin eggs. 891 2

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>