Nitric oxide (NO) is an endogenous vasodilator and inhaled NO is a promising therapeutic agent for the treatment of pulmonary hypertension. However, NO's mechanism of action is not completely understood. Previous studies have shown that NO increases intracellular levels of cyclic guanosine 3',5'-monophosphate (cGMP) and that leads to activation of calcium-gated potassium channels in vascular smooth muscle cells. Resulting cell membrane hyperpolarization causes vasorelaxation. The potassium channel activation by NO is inhibited by a blockade of cyclic nucleotide-dependent protein kinases, suggesting a key role of these enzymes in NO-induced vasodilation. To further examine this mechanism, we tested the hypothesis that pharmacological stimulation of the cGMP-dependent protein kinase will simulate the activating effect of NO on potassium channels. Indeed, we found that (Sp)-guanosine cyclic 3',5'-phosphorothioate (1 microM), a selective activator of the cGMP-dependent protein kinase, dramatically increased potassium currents measured by the whole-cell patch clamp technique in freshly dispersed pulmonary artery smooth muscle cells. These currents were inhibited by an inhibitor of calcium-gated potassium channels, charybdotoxin. Our results support the hypothesis that the effect of NO on potassium channels is mediated by the cGMP-dependent protein kinase.

• MeSH
• gating iontového kanálu účinky léků   MeSH
• guanosinmonofosfát cyklický farmakologie   MeSH
• krysa rodu Rattus MeSH
• membránové potenciály MeSH
• metoda terčíkového zámku MeSH
• oxid dusnatý farmakologie   MeSH
• potkani Sprague-Dawley MeSH
• proteinkinasy závislé na cyklickém GMP účinky léků   metabolismus   MeSH
• svaly hladké cévní účinky léků   metabolismus   MeSH
• vápníkové kanály účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• guanosinmonofosfát cyklický MeSH
• oxid dusnatý MeSH
• proteinkinasy závislé na cyklickém GMP MeSH
• vápníkové kanály MeSH

The assembly of ancient informational polymers from nucleotide precursors is the central challenge of life's origin on our planet. Among the possible solutions, dry polymerization of 3',5'-cyclic guanosine monophosphate (3',5'-cGMP) has been proposed as a candidate to create oligonucleotides of 15-20 units in length. However, the reported sensitivity of the reaction to the presence of cations raised questions of whether this chemistry could be relevant in a geological context. The experiments in this study show that the presence of cations is not restrictive as long as the reaction is conducted in an acidic environment, in contrast to previous reports that suggested optimal conditions at pH 9.

• Klíčová slova
• cGMP, nonenzymatic polymerization, nucleotides, prebiotic chemistry,
• MeSH
• guanosinmonofosfát cyklický * MeSH
• katalýza MeSH
• oligonukleotidy MeSH
• polymerizace MeSH
• RNA * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• guanosinmonofosfát cyklický * MeSH
• oligonukleotidy MeSH
• RNA * MeSH

Pig oocytes matured in vitro were parthenogenetically activated (78%) after treatment with 2 mM nitric oxide-donor (+/-)-S-nitroso-N-acetylpenicillamine (SNAP) for 24 h. Inhibition of soluble guanylyl cyclase with the specific inhibitors 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or 6-anilino-5,8-quinolinequinone (LY83583) suppressed the SNAP-induced activation in a dose-dependent manner (23% of activated oocytes after treatment with 400 microM ODQ; 12% of activated oocytes after treatment with 40 microM LY83583). 8-Bromo-cyclic guanosine monophosphate (8-Br-cGMP), a phosphodiesterase-resistant analogue of cGMP, enhances the effect of suboptimal doses (0.1 or 0.5 mM) of the NO donor SNAP. DT3, a specific inhibitor of cGMP-dependent protein kinase (PKG, PKG), is also able to inhibit the activation of pig oocytes after NO donor treatment. Involvement of the cGMP-dependent signalling pathway is specific for NO-induced oocyte activation, because both the guanylyl cyclase inhibitor ODQ and the PKG inhibitor DT3 are unable to inhibit activation in oocytes treated with the calcium ionophore A23187. These data indicate that the activation of pig oocytes with an NO donor is cGMP-dependent and that PKG plays an important role in this mode of oocyte activation.

• MeSH
• aktivace enzymů účinky léků   MeSH
• aminochinoliny metabolismus   farmakologie   MeSH
• chinoxaliny metabolismus   farmakologie   MeSH
• digitoxin metabolismus   farmakologie   MeSH
• fosfodiesterasy metabolismus   MeSH
• guanosinmonofosfát cyklický analogy a deriváty   metabolismus   farmakologie   MeSH
• guanylátcyklasa MeSH
• inhibitory proteinkinas metabolismus   farmakologie   MeSH
• oocyty cytologie   účinky léků   enzymologie   MeSH
• oxadiazoly metabolismus   farmakologie   MeSH
• oxid dusnatý metabolismus   MeSH
• penicilamin analogy a deriváty   metabolismus   farmakologie   MeSH
• permeabilita buněčné membrány účinky léků   MeSH
• prasata metabolismus   MeSH
• proteinkinasy závislé na cyklickém GMP antagonisté a inhibitory   metabolismus   MeSH
• receptory cytoplazmatické a nukleární metabolismus   MeSH
• rozpustná guanylátcyklasa MeSH
• signální transdukce * účinky léků   MeSH
• synthasa oxidu dusnatého metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one MeSH Prohlížeč
• 6-anilino-5,8-quinolinedione MeSH Prohlížeč
• 8-bromocyclic GMP MeSH Prohlížeč
• aminochinoliny MeSH
• chinoxaliny MeSH
• digitoxin MeSH
• fosfodiesterasy MeSH
• guanosinmonofosfát cyklický MeSH
• guanylátcyklasa MeSH
• inhibitory proteinkinas MeSH
• oxadiazoly MeSH
• oxid dusnatý MeSH
• penicilamin MeSH
• proteinkinasy závislé na cyklickém GMP MeSH
• receptory cytoplazmatické a nukleární MeSH
• rozpustná guanylátcyklasa MeSH
• S-nitro-N-acetylpenicillamine MeSH Prohlížeč
• synthasa oxidu dusnatého MeSH

Concentrations and mutual correlations of the cyclic adenosin monophosphate (cAMP), quanosin monophosphate (cGMP), progesterone (P4) and 17-beta-estradiol (E2) were studied in the fluid of the largest follicles in cows, in dependence on the steroid dominance: estrogen-dominant (ED), progesterone-dominant (PD) follicles. Mean cAMP and cGMP concentrations in the follicular fluid in the estrogen-dominant follicles were significantly higher than in the progesterone-dominant follicles; in both cases at P less than 0.01. Significant positive correlation between cAMP and cGMP at P less than 0.001 was stated in the evaluation of the correlations. The cAMP and cGMP concentrations were in significantly negative correlations with the P4 concentration at P less than 0.05, or P less than 0.01 and in significantly positive correlations with the E2, at P less than 0.05. The stated correlations suggest a close mutual relation between cyclic nucleotid and E2, or P4 when the follicles' quality changes.

• MeSH
• AMP cyklický analýza   MeSH
• estradiol analýza   MeSH
• guanosinmonofosfát cyklický analýza   MeSH
• ovariální folikul anatomie a histologie   chemie   MeSH
• progesteron analýza   MeSH
• skot metabolismus   MeSH
• zvířata MeSH
• Check Tag
• skot metabolismus   MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• AMP cyklický MeSH
• estradiol MeSH
• guanosinmonofosfát cyklický MeSH
• progesteron MeSH

• MeSH
• AMP cyklický krev   MeSH
• dospělí MeSH
• guanosinmonofosfát cyklický krev   MeSH
• hypertyreóza krev   MeSH
• hypotyreóza krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• AMP cyklický MeSH
• guanosinmonofosfát cyklický MeSH

The purpose of this study was to investigate plasma concentrations of cyclic guanosine monophosphate (cGMP) and atrial natriuretic peptide (ANP) during and after real and simulated space flight. Venous blood was obtained 3 min after the beginning and 2 min after the lower body negative pressure maneuver in two cosmonauts preflight (supine), inflight, and postflight (supine) and in five other subjects before, at the end, and 4 days after a 5-day head-down tilt (-6 degrees) bed rest. In cosmonaut 1 (10 days in space), plasma cGMP fell from preflight 4.3 to 1.4 nM on flight day 6, and was 3.0 nM on the fourth day after landing. In cosmonaut 2 (438 days in space), it fell from preflight 4.9 to 0.5 nM on on flight day 3, and stayed <0.1 nM with 5, 9, and 14 months in space, as well as on the fourth day after landing. Three months after the flight his plasma cGMP was back to normal (6.3 nM). Cosmonaut 2 also displayed relatively low inflight ANP values but returned to preflight level immediately after landing. In a ground-based simulation on five other persons, supine plasma cGMP was reduced by an average of 30% within 5 days of 6 degrees head-down tilt bed rest. The data consistently demonstrate lowered plasma cGMP with real and simulated weightlessness, and a complete disappearance of cGMP from plasma during, and shortly after long-duration space flight.

• MeSH
• abdominální dekomprese MeSH
• antikoagulancia krev   MeSH
• atriální natriuretický faktor krev   MeSH
• dospělí MeSH
• EDTA krev   MeSH
• guanosinmonofosfát cyklický krev   MeSH
• heparin krev   MeSH
• kosmický let * MeSH
• lidé MeSH
• supinační poloha MeSH
• Trendelenburgova poloha MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antikoagulancia MeSH
• atriální natriuretický faktor MeSH
• EDTA MeSH
• guanosinmonofosfát cyklický MeSH
• heparin MeSH

Male and female rats were given oestradiol benzoate (1 mg s.c. twice a week for 3 weeks) and/or sodium nitroprusside (SN), a donor of nitric oxide (NO), which was administered in their food in amounts of 0.2 or 0.6 mg/rat/day. Neither oestradiol-induced hypertrophy of the hypophysis, nor the serum prolactin (PRL) level, was affected by the simultaneous administration of SN. The PRL content of the hypophysis rose after oestradiol in the males, but the increase was again uninfluenced by the simultaneous administration of SN and the cAMP content of the hypophysis--raised after oestradiol--was likewise unaffected. The amount of cGMP in the hypophysis after oestradiol rose only in males. Both the serum and the hypophyseal prolactin level were found to be correlated to the cAMP and the cGMP content of the hypophysis. It was found that the simultaneous administration of SN together with oestradiol slightly reduced the increase in the cGMP content of the hypophysis elicited with oestradiol treatment only.

• MeSH
• AMP cyklický biosyntéza   MeSH
• estradiol farmakologie   MeSH
• guanosinmonofosfát cyklický biosyntéza   MeSH
• hypertrofie chemicky indukované   MeSH
• hypofýza účinky léků   metabolismus   patologie   MeSH
• krysa rodu Rattus MeSH
• nitroprusid farmakologie   MeSH
• potkani Wistar MeSH
• prolaktin krev   MeSH
• velikost orgánu MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• AMP cyklický MeSH
• estradiol MeSH
• guanosinmonofosfát cyklický MeSH
• nitroprusid MeSH
• prolaktin MeSH

Cyclic guanosine-3'5' monophosphate (cGMP) can mobilize intracellular calcium from the microsomal fraction of B-lymphocytes of the mouse spleen as a result of activation of cGMP-dependent microsomal proteinkinases. The existence of such a mechanism makes B-lymphocytes independent of extracellular calcium in response to agents whose effect on B-lymphocytes is mediated by calcium mechanisms.

• MeSH
• B-lymfocyty účinky léků   metabolismus   MeSH
• fosforylace MeSH
• guanosinmonofosfát cyklický farmakologie   MeSH
• mikrozomy účinky léků   enzymologie   metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• proteinkinasy metabolismus   MeSH
• sarkoplazmatické retikulum účinky léků   metabolismus   MeSH
• vápník metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• guanosinmonofosfát cyklický MeSH
• proteinkinasy MeSH
• vápník MeSH

Male rats received estradiol benzoate in a long acting microcrystalline suspension (1 mg/rat i.m., twice a week), methylene blue (MB) 0.5% in the food and the combination of estradiol and MB. After three weeks, MB partially inhibited the growth response of the anterior pituitary to estradiol and it partially inhibited the increase of cAMP content in anterior pituitary. The increase of anterior pituitary cGMP content was not modified by MB, neither the ratio cAMP/cGMP in the anterior pituitary which, however, decreased after estradiol. This decrease was not modified by MB. On the other hand, the prolactin (PRL) increase in the blood after estradiol was inhibited by MB, although the prolactin content in the anterior pituitary was not. Methylene blue alone did not change blood prolactin concentration, but it unexpectedly elevated blood thyroxine levels and this effect was partially inhibited by simultaneous estradiol treatment.

• MeSH
• adenohypofýza anatomie a histologie   účinky léků   metabolismus   MeSH
• AMP cyklický metabolismus   MeSH
• estradiol farmakologie   MeSH
• guanosinmonofosfát cyklický metabolismus   MeSH
• krysa rodu Rattus MeSH
• lékové interakce MeSH
• methylenová modř farmakologie   MeSH
• potkani Wistar MeSH
• prolaktin metabolismus   MeSH
• velikost orgánu MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• AMP cyklický MeSH
• estradiol MeSH
• guanosinmonofosfát cyklický MeSH
• methylenová modř MeSH
• prolaktin MeSH

Male rats received estradiol benzoate in a long acting microcrystalline suspension (1 mg/rat i.m., twice a week), methylene blue (MB) 0.5% in the food and the combination of estradiol and MB. After three weeks, MB partially inhibited the growth response of the anterior pituitary to estradiol and it partially inhibited the increase of cAMP content in anterior pituitary. The increase of anterior pituitary cGMP content was not modified by MB, neither the ratio cAMP/cGMP in the anterior pituitary which, however, decreased after estradiol. This decrease was not modified by MB. On the other hand, the prolactin (PRL) increase in the blood after estradiol was inhibited by MB, although the prolactin content in the anterior pituitary was not. Methylene blue alone did not change blood prolactin concentration, but it unexpectedly elevated blood thyroxine levels and this effect was partially inhibited by simultaneous estradiol treatment.

• MeSH
• adenohypofýza účinky léků   růst a vývoj   metabolismus   MeSH
• AMP cyklický biosyntéza   MeSH
• antagonisté estrogenu farmakologie   MeSH
• estradiol farmakologie   MeSH
• guanosinmonofosfát cyklický biosyntéza   MeSH
• krysa rodu Rattus MeSH
• methylenová modř farmakologie   MeSH
• potkani Wistar MeSH
• prolaktin biosyntéza   krev   MeSH
• radioimunoanalýza MeSH
• tělesná hmotnost účinky léků   MeSH
• thyroxin krev   MeSH
• velikost orgánu účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• AMP cyklický MeSH
• antagonisté estrogenu MeSH
• estradiol MeSH
• guanosinmonofosfát cyklický MeSH
• methylenová modř MeSH
• prolaktin MeSH
• thyroxin MeSH