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Biomedical subjects

S Iwasaki

Publications and source records attributed to S Iwasaki.

At least 91 records · Page 5Linked to original sources
PubMed1998

Natural organic compounds that affect to microtubule functions.

Microtubules (MT), composed of a protein tubulin (TN) alpha,beta-heterodimer with concomitant other proteins, microtubule associated proteins (MAPs and tau), are known to be the main component of spindles in a mitotic apparatus of eucaryotic cells, and are also involved in many other basic and essential cell functions. There are a number of natural and synthetic compounds that interfere with MT function to cause the mitotic arrest of eucaryotic cells. Such antimitotic agents show a broad biological activity, and can be used for medicinal and agrochemical purposes. On the other hand, they are also important as the biochemical tools for understanding the dynamics of MT network. Most of such antimitotic agents, with a few exceptions, bind to beta-TN. Among them, colchicine (CLC), vinblastine (VLB) and taxol have been of major importance in biochemical studies of MT and in studies of their intracellular functions. The former two both inhibit MT assembly but their binding sites on beta-TN are different; CLC-site and VLB-site, and many MT inhibitors bind to either sites. Taxol bind to TN at a site other than CLC-site and VLB-site, and promote MT assembly. We have worked on a variety of antimitotic agents that bind to CLC, VLB or taxol-site, in discoveries, structures, biological actions and/or interactions with TN. In this paper, I summarized the results of our studies on VLB-site ligands; (1) rhizoxin (RZX), isolated as a phytotoxin produced by a plant pathogenic fungus, and its related compounds, (2) derivatives of ansamitocin P-3 (ASMP3) (maytansinoid: MAY), isolated as a cytotoxic metabolite of an Actinomycete, (3) phomopsin A (PMSA), isolated as a mycotoxin produced by a plant parasitic fungus, (4) dolastatin 10 (DLS10), isolated as a cytotoxic metabolite of a see animal, (5) ustiloxins (USL) A-F, isolated as a mycotoxin produced by a plant pathogenic fungus, (6) arenastation A (ARSA), isolated as a cytotoxic metabolite of a sponge, and its synthetic analogs. From our studies on interactions of these VLB-site ligands with TN, we showed that the presence of a distinct RZX/MAY-binding site which only partially overlap with VLB-site, and that PMSA, DLS10, USLs and ARSA bind to the RZX/MAY site. RZX, ASMP3 and ARSA inhibit the growth of a variety of fungi, including Aspergillus nidulans. In order to obtain information as to the drug-TN interaction at the RZX/MAY site, RZX-resistant beta-TN gene mutants were isolated from RZX-sensitive wild-type A. nidulans. In all the beta-TN gene mutants, single amino acid (100th) alteration, asparagine-to-isoleucine, was observed. Sequence displacement experiments confirmed that this alteration conferred resistance to RZX and ASMP3, and also to ARSA. This resistance mechanism was further verified with yeasts Schizosaccharomyces pombe and Saccharomyces serevisiae. All the natural ligands mentioned above show potent cytotoxicity against human and murine tumor cells, but VLB, PMSA, DLS10 and USLA are inactive to both RZX-sensitive and -resistant fungal strains.

Animals↗
PubMed1997

Comparison of exocytotic mechanisms between acetylcholine- and catecholamine-containing vesicles in rat pheochromocytoma cells.

The molecular mechanisms of exocytosis from two types of secretory organelles, synaptic-like microvesicles and secretory vesicles, were compared by measuring acetylcholine (ACh) and catecholamine (CA) release from a newly isolated PC12 subclone, PC12-C3 which contains a high level of Ach. Digitonin-permeabilized PC12-C3 cells released both transmitters with similar Ca(2+)-dependency. Ca(2+)-evoked Ach and CA release from permeabilized cells were increased in the presence of MgATP, suggesting the existence of a MgATP-dependent priming step prior to the Ca(2+)-triggered fusion step in both ACh release and CA release. The non-hydrolyzable analogue of GTP guanosine 5'-(gamma-thio)triphosphate (GTP gamma S), produced both ACh and CA release from permeabilized cells in the absence of Ca2+. Pretreatment with a phorbol ester which activates protein kinase C, potentiated depolarization-induced ACh and CA release from unpermeabilized cells. These results indicated that exocytosis from two distinct vesicle populations are mediated by the same basic molecular mechanisms.

Acetylcholine↗
PubMed1997

Influences of dietary omega-3 polyunsaturated fatty acids on the recovery of cardiac and renal functions after preservation in hyperlipidemic rats.

BACKGROUND: The effects of a soybean oil diet and a high-cholesterol oil (HC) diet, and an HC diet with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) supplementation, on basal and postpreservative cardiac function of the hearts and on postpreservative renal function of the kidneys from older rats were examined. METHODS: Groups 1 through 4 of 100-week-old rats were fed either soybean oil, HC, HC with EPA, or HC with DHA, respectively, for 12 weeks. Blood was collected for analysis of plasma fatty acids, and the heart and left kidney were removed from the rat. In experiment 1, the heart was perfused on a Langendorff apparatus. After evaluation of the cardiac function of each rat, the heart was stored in histidine-tryptophan-ketoglutarate solution for 8 hr at 4 degrees C. The heart was reperfused and the recovery of cardiac function was evaluated. The coronary perfusate during reperfusion was collected to measure 6-keto prostaglandin F1alpha and thromboxane B2. Coronary flow (CF) perfused with Krebs-Henseleit bicarbonate (KHB) solution containing 5-hydroxytryptamine (5-HT) and nitroglycerin were evaluated in the Langendorff mode with atrial pacing (330 beats/min). In experiment 2, the excised left kidney was immediately flushed and preserved with University of Wisconsin solution for 8 hr at 4 degrees C. The kidney was then reperfused with KHB solution and renal function was evaluated. RESULTS: The plasma and cardiac EPA levels in group 3 were significantly higher than the levels found in the other groups. The plasma and cardiac ratios of EPA to arachidonic acid were significantly higher in groups 3 and 4 than in groups 1 and 2. There were no significant differences in basal cardiac function among any of the diet-fed rats. The percentage values of the recovery of aortic flow, cardiac output (CO), and left ventricular max dp/dt in group 3 and CO in group 4 were significantly higher than in group 2. In addition, the recovery of CF in group 3 tended to be higher than in group 2 (P=0.07). The percentage values of the recovery of aortic flow, CF, CO, and left ventricular max dp/dt in group 1 were significantly lower than in the other dietary groups. CF reperfused with KHB solution containing 5-HT was significantly higher in group 3 than in groups 1 and 2. CF reperfused with KHB solution containing 5-HT was significantly higher in group 4 than in group 1. CF reperfused with KHB solution containing nitroglycerin in group 3 tended to be higher than in groups 1 and 2 (P=0.07). The thromboxame B2 concentrations in the coronary perfusate during reperfusion in groups 3 and 4 were significantly lower than in groups 1 and 2. Fractional sodium reabsorption in group 3 was significantly higher than in group 2. Inulin clearance in groups 3 and 4 was significantly higher than in group 1. The postpreservative urinary flow in group 3 was significantly higher than in groups 1 and 2. The urinary flow was significantly higher in group 4 than in group 1. CONCLUSIONS: These results suggest that EPA administration may attenuate preservation and reperfusion injury and improve the recovery of cardiac and renal functions in hyperlipidemic and older rats. DHA administration may also show beneficial effects on kidney preservation in hyperlipidemic rats.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

A target of phosphatidylinositol 3,4,5-trisphosphate with a zinc finger motif similar to that of the ADP-ribosylation-factor GTPase-activating protein and two pleckstrin homology domains.

We have purified a protein that binds phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] using beads bearing a PtdIns(3,4,5)P3 analogue. This protein, with a molecular mass of 43 kDa, was termed PtdIns(3,4,5)P3-binding protein. The partial amino acid sequences were determined and a full-length cDNA encoding the protein was isolated from bovine brain cDNA library. The clone harbored an open reading frame of 373 amino acids which contained one zinc finger motif similar to that of ADP-ribosylation-factor GTPase-activating protein and two pleckstrin homology domains. The entire sequence was 83% similar to centaurin alpha, another PtdIns(3,4,5)P3-binding protein. The protein bound PtdIns(3,4,5)P3 with a higher affinity than it did inositol 1,3,4,5-tetrakisphosphate, phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4-bisphosphate, and phosphatidylinositol 3-phosphate suggesting that the binding to PtdIns(3,4,5)P3 was specific. The binding activity was weaker in the mutants with a point mutation in the conserved sequences in each pleckstrin homology domain. Introduction of both mutations abolished the activity. These results suggest that this new binding protein binds PtdIns(3,4,5)P3 through two pleckstrin domains present in the molecule.

ADP-Ribosylation Factors↗
PubMed1997

Ultrastructural study of the keratinization of the dorsal epithelium of the tongue of Middendorff's bean goose, Anser fabalis middendorffii (Anseres, Antidae).

BACKGROUND: Comparative studies of ultrastructural features of tongues allow deductions to be made about relationships between structure and function, as reflected by an animal's feeding habits. The present study was performed to serve as a basis for further studies of avian feeding mechanisms and of relationships between the fine structure of the lingual epithelium and the development of the expression of keratins. METHODS: The light microscope, scanning electron microscope, and transmission electron microscope were used. RESULTS: The dorsal surface of the tongue of Middendorff's bean goose, Anser fabalis middendorffii, has a distinctive anterior region that extends for five-sixths of its length and has a clear posterior region. The anterior region, when observed macroscopically and by scanning electron microscopy, is distinguished along its forward half by a clear median line. The back half of the anterior region has an indistinct median sulcus in some parts. There are no lingual papillae on the entire dorsal surface of the anterior and posterior regions. Giant conical papillae are located in a transverse row between the anterior and posterior regions. On both lateral sides of the anterior region for five-sixths of the length of the tongue, lingual hairs are compactly distributed, and small numbers of large cylindrical papillae are arranged at almost regular intervals between these lingual hairs. Examination of the dorsal lingual epithelium by light and transmission electron microscopy provided histological and cytological criteria for distinguishing the anterior and posterior regions, both of which were composed of stratified squamous epithelium. Basal cells were similar throughout the dorsal epithelium. The intermediate layer of cells in the anterior region contained numerous tonofibrils in electron-dense bundles composed of tonofilaments of 10 nm in diameter. The outer layer was composed of electron-dense, well-keratinized cells, with layers of electron-lucent cells on the outermost surface. The cells in the intermediate layer in the posterior region of the tongue were almost completely filled with unbundled tonofilaments. The surface layer exhibited features of parakeratinization. In all of the giant conical papillae, the large cylindrical papillae, and the lingual hairs, the epithelium was strongly keratinized. CONCLUSIONS: The three-dimensional microanatomy and cytological features of the dorsal lingual epithelium of avians seem to be related to the functional role and shape of the tongue of each species in feeding.

Age Factors↗
PubMed1997

Study by scanning electron microscopy of the morphogenesis of three types of lingual papilla in the rat.

BACKGROUND: Many mammals have four different types of lingual papilla, namely filiform, fungiform, circumvallate, and foliate papillae, on the dorsal or lateral surface of the tongue. However, details of the morphogenesis of these lingual papillae have not been reported. We have investigated the changes in the three-dimensional ultrastructure that occur during the morphogenesis of filiform, fungiform, and circumvallate papillae in rats during fetal and postnatal development. METHODS: Tongues were removed from rat fetuses on days 12 (E12) and 16 (E16) of gestation from newborns (P0) and from juveniles on days 7 (P7) and 14 (P14), and 21 (P21) after birth. Scanning electron microscopy was used for all observations. RESULTS: In fetuses at E12, the rudiments of fungiform papillae could be observed as two rows of bulges that extended bilaterally and parallel to the median sulcus on the anterior half of the dorsal surface of the tongue. In fetuses at E16, the arrangement of the rudiments of fungiform papillae was relatively regular, with a latticelike pattern. At this stage, the outline of the rudiment of the circumvallate papilla could be recognized on the median line between the lingual body and the lingual radix. No rudiments of filiform papillae were visible. At P0, rudiments of filiform papillae were compactly distributed over the dorsal surface in the same way as in the adult. The width of these rudiments was about one-fourth that of fungiform papillae, and their tips were round as compared with those of filiform papillae in the adult. The fungiform and circumvallate papillae were large, and their outlines were somewhat irregular, as in the adult. In juveniles at P7, filiform papillae were long and slender. On the intermolar eminence, filiform papillar structures were quite large. A taste pore was clearly visible at the center of each fungiform papilla at this stage. The shape of the circumvallate papilla was similar to that in the adult. In juveniles at P14 and P21, the shapes of all three types of papilla were almost same as those in the adult. CONCLUSIONS: The rudiments of each of the three different kinds of lingual papilla appeared at a different respective stage of development in rats. The rudiments of the fungiform and circumvallate papillae, which are related to the sense of taste, were visible earlier than those of the filiform papillae, which are not involved in this sense.

Age Factors↗
PubMed1997

Experimental investigation of the role of the splenic vein in gastric venous obstruction after pylorus-preserving pancreatoduodenectomy in the dog.

CONCLUSION: This study showed that the splenic vein (SV) plays a major role in maintaining gastric blood flow after ligature of peripyloric vessels in the dog. Therefore, SV preservation or alternative venous drainage may be recommended to maintain sufficient gastric blood flow in pylorus-preserving pancreatoduodenectomy (PPPD). BACKGROUND: In PPPD, we often encounter the problem of gastric venous drainage obstruction, if the splenic-portal vein confluence needs to be resected. This study investigated significance of venous drainage via the left gastric and splenic veins in gastric tissue blood flow. METHODS: In seven mongrel dogs, gastric tissue blood flow was measured by both laser Doppler flowmetry (LDF) in the antrum and hydrogen gas clearance (HGC) in the antrum and body. Blood flow was measured after the following treatments: 1. No treatment; 2. Duodenal transection; 3. Ligature of the right gastric and gastroepiploic arteries and veins; 4. Transient obstruction of the left gastric vein (LGV); 5. Transient obstruction of the SV with the LGV open; and 6. Obstruction of both the LGV and the SV. RESULTS: As judged by LDF, treatments 2, 3, and 4 did not decrease blood flow, but treatments 5 and 6 significantly decreased it compared with both treatments 1 and 3. By HGC, changes in the antrum and the body were parallel. Duodenal transection did not, but treatments 3 and 4 did decrease blood flow compared with no treatment. Obstruction of the left gastric vein did not, but treatments 5 and 6 did significantly decrease it compared with treatment 3.

Animals↗
PubMed1997

Histological and ultrastructural study of the effects of cholinergic and adrenergic agonists on salivary secretion from the lingual epithelium and the lingual gland of the Tokyo Daruma pond frog.

Comparative observations of the effects of cholinergic and adrenergic agonists (such as pilocarpine, phenylephrine and isoproterenol) on the secretion of salivary fluid and of secretory granules from the lingual epithelium and the lingual gland in the Tokyo Daruma pond frog, Rana porosa porosa, were made by light and transmission electron microscopy. The effect of pilocarpine on the loss of cytoplasm in both the lingual epithelium and the lingual gland was the strongest, and that of isoproterenol was the weakest. Transmission electron microscopy revealed that electron-dense granules, located in cells in both the lingual epithelium and the lingual gland, were discharged by exocytosis after stimulation by phenylephrine and isoproterenol. Immediately before secretion of these granules, they became somewhat larger and round or distorted in shape. However, after administration of pilocarpine, no obvious discharge of electron-dense granules was apparent and, instead, granules in some cells began deteriorating within the cells and those in other cells developed electron-dense and electron-lucent areas. A dot-like pattern was recognized in the electron-dense areas of these granules. These phenomena were assumed to be secondary effects accompanying the secretion of salivary fluid from cells of the lingual epithelium and the lingual gland. By contrast, mucous granules in the lingual gland were secreted by a holocrine process.

Adrenergic alpha-Agonists↗
PubMed1997

Bromocriptine enhances feeding behavior without changing dopamine metabolism.

Bromocriptine is an ergot derivative and has been thought to act as a selective D2 receptor agonist, but its effects on dopamine release in vivo have not been confirmed. We administered bromocriptine into the striatum of rats and studied the effects on feeding behavior and dopamine release. Bromocriptine was perfused via a microdialysis probe into the ventrolateral striatum of rats fasted for 22 h, and the rats were then allowed to feed freely for 6 h. Bromocriptine perfusion increased food intake in a dose-dependent manner, whereas the extracellular concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) did not change. Perfusion of (-) sulpiride, a selective D2 receptor antagonist, decreased food intake, but increased dopamine release and the levels of DOPAC and HVA. Pretreatment with (-)sulpiride perfusion for 1 h prior to bromocriptine perfusion inhibited the increase of food intake induced by bromocriptine, and it increased dopamine release and the levels of DOPAC and HVA. These findings suggest that bromocriptine directly perfused into the ventrolateral striatum acts selectively on postsynaptic D2 receptors and enhances feeding behavior.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Identification of an autoantibody against alpha-enolase in primary biliary cirrhosis.

BACKGROUND: Primary biliary cirrhosis is a chronic cholestatic liver disease in which autoreactive T cells may play an important role in the destruction of intrahepatic bile ducts. However, target antigens remain unknown. Alpha-enolase-derived peptide binds to human leukocyte antigen (HLA)-DR8, which is implicated in the development of primary biliary cirrhosis in Japanese patients. Partial homology between alpha-enolase and the inner lipoyl domain of E2 component of pyruvate dehydrogenase (PDH-E2) is also observed. METHODS: Using alpha, beta and gamma enolase isozymes obtained from humans and/or rabbits, we examined serum samples of 56 patients with primary biliary cirrhosis, 19 autoimmune hepatitis, 38 acute and chronic viral hepatitis and 36 healthy subjects by immunoblotting. RESULTS: Anti-alpha-enolase antibody was present in a significantly higher percentage of patients with primary biliary cirrhosis (16 of 56, 28.6%) and autoimmune hepatitis (6 of 19, 31.6%) than in normal subjects (p<0.005, p<0.01, respectively). Antibodies against beta and gamma-enolases were not detected in any serum sample. Although there was no significant correlation between the presence of anti-alpha-enolase antibody and clinical features of primary biliary cirrhosis, the mortality rate associated with hepatic failure in patients with positive autoantibody was significantly higher than that of antibody-negative PBC patients (6 of 16, 37.5% vs 5 of 40, 12.5%, p<0.05). CONCLUSIONS: Since alpha-enolase is expressed on the cell surface, our data suggest that the immunological reaction to alpha-enolase might be involved in biliary epithelial destruction and be relevant to the disease progression.

Acute Disease↗
PubMed1997

Elimination study of silver in a hemodialyzed burn patient treated with silver sulfadiazine cream.

Silver sulfadiazine (SSD) cream is a potent agent for the treatment of burns. In a patient with end-stage renal disease, we observed a marked elevation in serum silver concentration in the course of 2 weeks of SSD cream therapy (200 g/d). Serum concentration of silver reached a maximum of 291 ng/mL in association with a rapid deterioration of mental status. SSD therapy was discontinued, and hemodialysis, hemofiltration, or plasma exchange was continually performed. Four months later, the patient died. At autopsy, profoundly elevated levels of silver were found in brain tissues of this patient (617.3, 823.7 ng/g wet tissue weight in the cerebrum and cerebellum, respectively). To determine the most efficient therapy to remove silver from serum, we compared hemodialysis (HD), hemofiltration (HF), and plasma exchange (PE). Both plasma exchange and hemofiltration were effective in decreasing serum silver, and their effects were additive. By contrast, HD was ineffective in reducing serum silver. This case illustrates that, on SSD cream therapy, burn patients with disturbed renal function are at risk of accumulating silver in serum and tissue to the level that may cause neuralgic decompensation. Removal of serum silver can best be effected by PE, particularly when combined with HF. In contrast, HD per se does not appear efficacious. None of these blood purification modalities improves deterioration of neurological status potentially attributable to silver deposition in brain tissues.

Adult↗
PubMed1997

Focal microcirculation disorder induced by photochemical reaction in the guinea pig cochlea.

A small region of microcirculation disorder in the cochlea of the guinea pig could be induced by a photochemical reaction. Photoillumination to the cochlea was done after systemic infusion of Rose Bengal (RB). The lateral wall of the second or third turn of the cochlea was illuminated for 10 min with a 1 mm diameter focused green light supplied by a xenon lamp. Degeneration of the stria vascularis (SV) was observed by a scanning electron microscope at 60-300 min after illumination. The range of length of degenerated area in the SV was from 111 to 1800 microns, with a mean of 760 microns. The organ of Corti along the illuminated lesion of the SV was well preserved in all animals at 60-300 min. In contrast, degeneration of sensory hair cells and scar formation in the SV were observed in the focal lesions of the three animals killed 1 week after illumination. The increase of diameter in the vessel of the SV from the radiating arteriole, the vessel of basilar membrane (VSBM) and limbus vessel (LVS) were observed in the illuminated area with diaminobenzidine (DAB) staining. These findings suggest that segmental microcirculation damage occurred in the SV and modiolus. In physiological studies, compound action potentials (CAP) were evaluated. Endocochlear potentials (EP) were also measured at the second turn under three different situations (groups A, B and C). A photochemically induced lesion was created at the site of EP measurement (group A), a site in the second turn 1 mm from the EP measurement site (group B) and a site in the third turn adjacent to the EP measurement site (group C). Threshold shift of CAP (up to 5.6 +/- 1.8 dB SPL) and reduction of EP (down to 11.4 +/- 10.7 mV) in the photochemically injured location were detected during about 15 min. EP did not recover to the predamaged level (79.9 +/- 3.7 mV) during 20 min. The morphological and physiological changes were not observed in the control group with illumination only. There were no significant decreases in EP values at the sites 1 mm from the lesion (group B) and at the inferior turn adjacent to the lesion (group C) compared to the marked decrease at the site of the photochemically induced lesion (group A). These findings suggest that CAP and EP are significantly affected by the interruption of segmental blood supply in the cochlea and remarkable decrease of EP occurs in the focal region of the guinea pig cochlea. We conclude that a localized blood circulation disorder induced by the photochemical reaction can make a focal lesion in guinea pig cochlea morphologically and physiologically.

Action Potentials↗
PubMed1997

Temporal bone pathology of acoustic neuroma correlating with presence of electrocochleography and absence of auditory brainstem response.

The temporal bone pathology of a 74-year-old female affected by vestibular schwannoma was compared with findings of auditory brainstem response and electrocochleography. At age 71, she complained of hearing loss in the left ear in which pure tone audiometry revealed threshold elevation in the middle- and high-frequency range. Temporal bone CT scanning revealed a medium-sized cerebellopontine angle tumour in the left ear. ABR showed no response in the left ear, but the electrocochleography showed clear compound action potentials. Three years later, at age 74, she died of metastatic lung cancer and sepsis. The left temporal bone pathology consisted primarily of a large vestibular schwannoma occupying the internal auditory meatus. The organ of Corti was well preserved in each turn. In the modiolus, the numbers of spiral ganglion cells and cochlear nerve fibres in each turn were decreased. These histological findings suggest that clear compound action potentials were recorded from the distal portion of the cochlear nerve in spite of the presence of the vestibular schwannoma, but ABR could not be detected because of the blockade of the proximal portion of the cochlear nerve by the vestibular schwannoma.

Aged↗
PubMed1997

Inhibition of angiogenesis by rhizoxin, a microbial metabolite containing two epoxide groups.

Previous studies by our and other groups have shown that microbial products containing more than one epoxide group, including eponemycin, radicicol, depudecin and AGM-1470, exhibits anti-angio-genic activity in an in vivo assay system involving chorioallantoic membranes (CAMs) of growing chick embryos. Based on these findings, rhizoxin, a microbial metabolite that contains two epoxide groups and exhibits anti-tubulin activity, was tested for anti-angiogenic activity in a CAM assay system. Rhizoxin caused dose-dependent inhibition of embryonic angiogenesis, the ID50 value being 2 ng (3.2 pmol) per egg. In addition, this compound (2 mg/kg i.p.) significantly suppressed neovascularization induced by M5076 mouse tumor cells in a mouse dorsal air sac assay system, compared to the vehicle alone (P < 0.05). These results indicate that rhizoxin is a novel inhibitor of angiogenesis, and that is has potential as a new therapeutic agent for cancer.

Animals↗
PubMed1997

Effects of nitric oxide on ovulation and ovarian steroidogenesis and prostaglandin production in the rabbit.

Evidence supports the involvement of nitric oxide (NO) in ovarian physiology. The present study was undertaken to investigate the role of the NO/NO synthase (NOS) systems in ovulation, oocyte maturation, ovarian steroidogenesis, and PG production using in vitro perfused rabbit ovaries. The addition of the NOS inhibitors, aminoguanidine hemisulfate salt (AG) and N-omega-nitro-L-arginine methyl ester (L-NAME), to the perfusate inhibited the ovulation induced by hCG in a dose-dependent manner, whereas D-NAME had no significant effect. Neither AG nor L-NAME affected the hCG-induced meiotic maturation of the ovulated ova. The exogenous administration of the NO generator, sodium nitroprusside (NP), induced follicle rupture in the absence of gonadotropin, but did not induce oocyte maturation. Inhibition of endogenous NOS by AG and L-NAME resulted in a significant elevation in the production of estradiol (E2), but not of progesterone, stimulated by hCG. The concomitant administration of NP significantly reduced the AG-stimulated production of E2 by ovaries perfused in the presence of hCG, which suggests that NO down-regulates ovarian E2 synthesis. Ovarian production of PGE2 and PGF2alpha in response to hCG was significantly blocked by L-NAME, and exogenous administration of NP stimulated the production of PGs in the absence of gonadotropin. Significant correlations were observed between the ovulatory efficiencies and the production of PGs by rabbit ovaries perfused with or without L-NAME. In conclusion, the ovarian NO/NOS system is involved in follicle rupture during the ovulatory process. NO may induce follicle rupture in rabbit ovaries at least in part by the stimulation of PG production.

Animals↗