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A Hidalgo

Publications and source records attributed to A Hidalgo.

At least 55 records · Page 3Linked to original sources
PubMed2000

Glia dictate pioneer axon trajectories in the Drosophila embryonic CNS.

Whereas considerable progress has been made in understanding the molecular mechanisms of axon guidance across the midline, it is still unclear how the axonal trajectories of longitudinal pioneer neurons, which never cross the midline, are established. Here we show that longitudinal glia of the embryonic Drosophila CNS direct formation of pioneer axon pathways. By ablation and analysis of glial cells missing mutants, we demonstrate that glia are required for two kinds of processes. Firstly, glia are required for growth cone guidance, although this requirement is not absolute. We show that the route of extending growth cones is rich in neuronal cell bodies and glia, and also in long processes from both these cell types. Interactions between neurons, glia and their long processes orient extending growth cones. Secondly, glia direct the fasciculation and defasciculation of axons, which pattern the pioneer pathways. Together these events are essential for the selective fasciculation of follower axons along the longitudinal pathways.

Animals↗
PubMed2000

Effects of intraplantar morphine in the mouse formalin test.

We studied the effects of intraplantar morphine in the formalin test in mice. Intraplantarly administered morphine (30 - 300 microg) induced analgesic effects at lower doses than intraperitoneally administered morphine. Following the administration of [3H]morphine, the % of radioactivity present in brain was the same by either route. In contrast, higher radioactivity values appeared in the injected paw in those mice intraplantarly injected. Since local morphine induces analgesia at doses lower than the intraperitoneally administered drug, especially in the second phase of the test, and the access to brain is undistinguishable, we propose that local morphine enhances central opiate analgesia in the formalin test in mice.

Analgesics, Opioid↗
PubMed2000

Effects of DAGO on the rodent hippocampal evoked potentials using different perfusion solutions.

Opioid receptor agonists exert excitatory effects in the hippocampus by inhibiting GABA release. We report that the mu-opioid agonist, DAGO, increases the amplitude of the population spikes (PS) measured in the stratum pyramidale of the CA1 cell layer in mouse and rat hippocampal slices perfused with an artificial cerebrospinal fluid (ACSF), but not when perfused in Krebs solution. The GABAA agonist, 3-APS, induces inhibitory responses when perfused in either ACSF or Krebs. Also, the field excitatory postsynaptic potentials (EPSP) measured on stratum radiatum do not differ when the slice is perfused with either ACSF or Krebs. The increase in the amplitude of the PS induced by DAGO is not obtained when perfused in a modified. ACSF whose concentration of MgSO4 was lowered to its concentration in the Krebs solution (from 2.4 mM to 1.2 mM). Thus, changes in the concentration of MgSO4 seem to be responsible for the different responses induced by DAGO.

Analgesics↗
PubMed1999

Fibrin glue reduces the severity of intra-abdominal adhesions in a rat model.

BACKGROUND: The purpose of this study was to determine whether fibrin glue inhibits intra-abdominal adhesions. METHODS: Twenty rats underwent midline laparotomy. To maximize adhesions, bilateral peritoneal muscular defects were created and covered with polypropylene mesh sewn with a braided suture. The bowel was abraded with dry gauze. Rats were randomized to either fibrin glue (FG) sprayed over the mesh or to control (no further treatment) groups. At 1 week, the adhesion density (graded 0 to 3), the percentage of the patch covered by adhesion (0% to 100%), and adhesion type were recorded. RESULTS: The mean adhesion density was 1.45+/-0.33 for FG versus 2.8+/-0.11 for controls (P = 0.001). The mean percentage of adhesions was 36+/-9.9 for the FG group and 94+/-3.7 for controls (P = 0.0002). Bowel or solid organs were adherent to the patch in 6 of 20 (30%) in the FG group versus 12 of 20 (70%) in controls (P = 0.057). CONCLUSIONS: Topical fibrin glue reduces the density and severity of intra-abdominal adhesions in a rat model.

Animals↗
PubMed1999

Role of genomic mechanisms on cAMP-dependent positive inotropism in isolated left atrium of rat.

It is well known that beta-adrenoceptor stimulation induces positive inotropism by cAMP-dependent phosphorylation of cardiac calcium channels. Furthermore, hypertrophy of different tissues including the heart have been related to the stimulation of these adrenoceptors via mechanisms coupled to activation of transcription and protein synthesis. Early effects of isoproterenol mediated via this pathway has also been associated to the stimulation of beta-adrenoceptors. However, the effects on the inotropism through genomic mechanisms have not yet been described. Isoproterenol (3 nM to 3 microM) induced a concentration-dependent positive inotropism, in isolated left atrium of male Wistar rats electrically stimulated (0.5 Hz, 5 ms, 30-50% above the threshold voltage), which was antagonized by atenolol (1 microM) and inhibited by a protein kinase A inhibitor, (R)p-cAMPS (10 microM). The inhibitor of transcription, actinomycin D (4 microM), and the protein synthesis inhibitor, cycloheximide (35.5 microM), significantly decreased the positive inotropism induced by isoproterenol. Forskolin (0.1 to 3 microM), an activator of adenylyl cyclase, induced a concentration-dependent positive inotropism which was also inhibited by (R)p-cAMPS, actinomycin D and cycloheximide. In the left atrium of rat, isoproterenol induced a positive inotropism which seems, at least in part, dependent upon intact transcription and protein synthesis, as suggested by the fact that the response was inhibited by the incubation with actinomycin D and cycloheximide. In addition, this genomic effect seems to be mediated by a cAMP-dependent mechanism. As it was inhibited by a protein kinase A inhibitor ((R)p-cAMPS) and similarly to isoproterenol, the positive inotropism induced by forskolin, which increases cytosolic cAMP, was also inhibited by actinomycin D and cycloheximide.

Adrenergic beta-Agonists↗
PubMed1999

Positive inotropism induced by androgens in isolated left atrium of rat: evidence for a cAMP-dependent transcriptional mechanism.

Steroid hormones exert their biological actions via intracellular receptors modulation of transcription. In addition, a number of molecular interactions, and the existence of membrane receptors in several tissues, support the hypothesis of nongenomic action of steroids. The androgens, 5alpha- and 5beta-dihydrotestosterone (0.1 to 100 microM), induce a rapid positive inotropism in the isolated left atrium of male Wistar rats whose time course of response might suggest that it is a non-genomic effect. However, the fact that the facilitation of contractility was inhibited by actinomycin D (5 microg/ml) and cycloheximide (10 microg/ml) indicates that a transcriptional component might play a role. The existence of a rapid functional genomic role would be somewhat surprising. However, rapid transcriptional mechanisms were also observed in certain cAMP-dependent responses. In the left atrium of rat, Rp-cAMPS (10 microM), a cAMP-dependent protein kinase inhibitor, antagonized 5alpha- but not 5beta-dihydrotestosterone-induced positive inotropism. The inhibition by Rp-cAMPS of isoproterenol- and forskolin-induced positive inotropism, and the fact that these cAMP-dependent effects were also inhibited by actinomycin D and cycloheximide, suggest that a cAMP-dependent transcriptional component may be partly involved in the positive inotropism induced by 5alpha-dihydrotestosterone. In addition, 5alpha-dihydrotestosterone might increase the basal adenylyl cyclase activity by acting on unoccupied beta-adrenoceptor-G-protein-adenylyl cyclase complexes, since the elicited inotropism was inhibited by a beta-blocker, atenolol (1 microM), a G-protein inhibitor, pertussis toxin (2 microg/ml, 3 h), and an adenylyl cyclase inhibitor, dideoxy-adenosine (10 microM).

Adenylate Cyclase Toxin↗
PubMed1999

Effects of diethylstilbestrol on mouse hippocampal evoked potentials in vitro.

1. Several steroids and related compounds can bind to central opiate receptors in whole-brain mouse homogenates. Among these drugs, the synthetic estrogen, diethylstilbestrol (DES), exhibits one of the highest affinities in binding experiments labeling opiate receptors with the nonselective opiate antagonist, [3H]diprenorphine. 2. In the search for a functional correlate to this biochemical finding, we have studied the effects of DES on the mouse hippocampal slice in vitro preparation. 3. Previously, binding studies were performed in hippocampal homogenates, labeling opiate receptors with [3H]diprenorphine or with the mu-selective opiate agonist, [3H]DAGO. DES inhibited [3H]diprenorphine and [3H]DAGO binding, the IC50 values obtained being (1.03 +/- 0.16) x 10(-5) and (1 +/- 0.8) x 10(-5) M, respectively. 4. In mice hippocampal slices, we measured the extracellular evoked potentials obtained in the CA1 pyramidal cell layer of the hippocampi and the field excitatory postsynaptic potentials (EPSP) obtained in the stratum radiatum. The presence of DES (10(-5) M) induced an increase in the amplitude of the population spikes measured in the pyramidal layer without modifying the field EPSP. This effect is similar to that obtained in the presence of DAGO in this preparation. The effect produced by DES was not modified by the presence of the opiate competitive antagonist, naloxone (10(-5) M), or by the opiate alkylating agent, beta-chlornaltrexamine (10(-5) M). Conversely, in the presence of the transcription inhibitor, actinomycin D (5 micrograms/ml), the effect produced by DES was inhibited. 5. Our results with DES support the general idea that estrogens increase central excitability. Although diethylstilbestrol can bind to opiate receptors in the hippocampus, the effect induced by this estrogen on hippocampal excitability seems unrelated to a direct action on opiate receptors, and an intracellular effect is suggested.

Animals↗
PubMed1999

Selective eosinophil transendothelial migration triggered by eotaxin via modulation of Mac-1/ICAM-1 and VLA-4/VCAM-1 interactions.

We have recently cloned eotaxin, a highly efficacious eosinophilic chemokine involved in the development of lung eosinophilia during allergic inflammatory reactions. To understand more precisely how eotaxin facilitates the specific migration of eosinophils, we have studied which adhesion receptors are essential for eotaxin action both in vivo and in vitro. Experiments using mice genetically deficient in adhesion receptors demonstrated that molecules previously reported to be involved in both leukocyte tethering/rolling (P-selectin and E-selectin) and in sticking/ transmigration (ICAM-1 and VCAM-1) are required for eotaxin action in vivo. To further elucidate the mechanism(s) involved in this process, we have used an in vitro transendothelial chemotaxis model. mAb neutralization studies performed in this system suggest that the integrins Mac-1 (CD11b/18), VLA-4 (alpha4beta1) and LFA-1 (CD11a/18) are involved in the transendothelial chemotaxis of eosinophils to eotaxin. Accordingly, the expression of these integrins on eosinophils is elevated by direct action of this chemokine in a concentration-dependent manner. Taken together, our results suggest that eotaxin-induced eosinophil transendothelial migration in vivo and in vitro relies on Mac-1/ICAM-1 and VLA-4NCAM-1 interactions, the latter ones becoming more relevant at later time points of the eotaxin-induced recruitment process.

Animals↗
PubMed1999

Involvement of cAMP and beta-adrenoceptors in the relaxing effect elicited by flavonoids on rat uterine smooth muscle.

1. The effect of the flavonoids genistein (3-100 microM), kaempferol (3-60 microM) and quercetin (1-100 microM) on KCl (60 mM)-induced tonic contraction in rat smooth muscle was assayed. In the same way, the modification of these effects in the presence of an inhibitor of protein kinase (PKA) (Rp-cAMPS), an inhibitor of phosphodiesterase (papaverine) and beta-adrenoreceptor blocking agents (propranolol and atenolol) was studied. 2. The flavonoids totally relaxed the KCl-induced tonic contraction (IC50: genistein 20.2 +/- 2.0 microM, n = 11; kaempferol 10.1 +/- 1.6 microM, n = 8; quercetin 13.2 +/- 1.2 microM, n = 8). 3. The incubation with Rp-cAMPS (10 and 100 microM) 30 min prior to KCl shifted the dose-response curve of the flavonoids to the right, increasing their IC50 up to 27.8 +/- 3.8 and 31.9 +/- 7.3 microM, respectively, for genistein; 24.7 +/- 0.2 and 19.6 +/- 4.9 microM, respectively, for kaempferol; 18.8 +/- 2.2 and 18.4 +/- 1.5 microM, respectively, for quercetin. 4. Papaverine (3-100 microM) also relaxed the contraction induced by KCl and this effect was significantly displaced to the right with Rp-cAMPS (10 microM) (IC50 12.1 +/- 2.2 vs. 16.5 +/- 3.1 microM). Papaverine (3 microM) added to the organ bath 15 min before the contractile agent increased the relaxing effect of the flavonoids and significantly decreased their IC50 (genistein 20.2 +/- 2.0 vs. 9.8 +/- 1.4 microM; kaempferol 10.1 +/- 1.6 vs. 6.6 +/- 0.7 microM; quercetin 13.2 +/- 1.2 vs. 7.8 +/- 1.4 microM). 5. The incubation with atenolol (10 microM) did not alter the relaxing effect of the flavonoids. In the same experimental conditions, propranolol (10 microM) did not modify the effect of genistein and kaempferol, but shifted the response curve of quercetin significantly to the right (13.2 +/- 1.2 vs. 17.7 +/- 3.4 microM). 6. The results suggest that genistein, kaempferol and quercetin produced the relaxation of uterine smooth muscle by increasing intracellular cAMP. Beta-adrenoceptors could also be involved in the effect of quercetin.

Animals↗
PubMed1999

Spinal effects of the calmodulin inhibitor calmidazolium on dorsal horn neurons in the rat.

Drugs able to inhibit calmodulin activation can prevent some consequences of the rise in intracellular calcium. It has recently been shown that intrathecal injection of calmodulin inhibitors induce analgesia in rats. We study here the effect induced by the calmodulin inhibitor, calmidazolium, on the activity of dorsal horn neurons driven by noxious and non-noxious stimuli. Extracellular recordings of convergent (n = 12), low-threshold mechanoreceptive (n = 5) and proprioceptive (n = 5) units were made in the presence of calmidazolium. Calmidazolium (600 micrograms) reduced the noxious (50 degrees C) heat-evoked responses obtained in convergent neurons. On the contrary, the non-noxious tactile responses obtained in low-threshold mechanoreceptive neurons as well as the joint movement-evoked responses obtained in proprioceptive units remained unmodified. We conclude that calmidazolium can block nociceptive processing in the spinal cord and that this fact can help to explain the analgesic effects that intrathecal W-7 and calmidazolium induce in behavioral tests.

Animals↗
PubMed1999

Study of the density of opioid receptors in the male mouse brain at different stages of sexual maturation.

The binding of opiate receptors was evaluated in male Swiss CD1 mice in different stages of maturation, i.e., prepubertal (7 and 20 days old), pubertal (40 days old) and postpubertal (60 days old). The opiate receptors were labeled with [3H]-diprenorphine and the KD and Bmax were measured. A similar KD (0.35-0.42 nM) value was obtained in all age groups tested indicating no changes in opiate affinity with sexual maturation. The maximal opiate binding capacity, Bmax was similar in 20- and 40-day-old mice as compared to 60-day-old mice while lower values were obtained in 7-day-old mice. These data indicate that sexual maturation does not affect the number of opiate receptors. Since different testosterone plasma levels have been described in males of this strain at the different ages included in our study, our results support previous findings showing that testosterone does not influence opiate binding sites in rodents.

Animals↗
PubMed1998

Pharmacological evidence for a receptor mediating sustained nucleotide-evoked contractions of rat aorta in the presence of UTP.

The contractile effect of ATP given alone or in the presence of other nucleotides was studied in rat aortic strips. A sustained contraction in response to ATP (30 microM to 10 mM) was observed during UTP exposure instead of the fast transient contraction produced via P2x purinoceptor activation in the absence of UTP, and contrary to the relaxation elicited when the tone had been raised by noradrenaline and KCl. This sustained ATP effect was produced in the smooth muscle and not via the same mechanism through which UTP elicited contraction, since the contractions in response to UTP and ATP were additive. They were also coupled to different transduction pathways: the effect of UTP but not that of ATP was pertussis toxin-sensitive. In contrast to the fast transient ATP contraction during basal tone, the sustained response was not desensitized by alpha,beta-methylene ATP exposure (30 microM), but was inhibited by reactive blue 2 (10 and 30 microM). Among the nucleotides assayed, UDP and ATPgammaS also enabled ATP to elicit a sustained contraction. ADP, AMP, dATP, 2-methylthio ATP, alpha,beta-methylene ATP, GTP, GDP, GMP, CTP and ITP also induced a sustained contraction in the presence of UTP. However, adenosine (1 mM) and adenine (0.3 to 3 mM) induced relaxation when the tone had been raised by UTP. According to these results a non-selective nucleotide receptor, different from the P2 purinoceptors functionally characterized so far, seems to mediate sustained contractions in rat aortic strips in the presence of UTP, UDP or ATPgammaS.

Adenosine Triphosphate↗
PubMed1998

Differential use of very late antigen-4 and -5 integrins by hematopoietic precursors and myeloma cells to adhere to transforming growth factor-beta1-treated bone marrow stroma.

The very late antigen (VLA)-4 and VLA-5 integrins mediate hematopoietic progenitor cell attachment to bone marrow (BM) stroma. Transforming growth factor-beta1 (TGF-beta1) is a cytokine present in the BM microenvironment that has been shown to regulate the synthesis of adhesion elements in several cell types. We have investigated whether TGF-beta1 action on human BM stromal cells affected the adhesion of progenitor cells involving integrins VLA-4 and VLA-5. Two precursor cell lines, pre-B Nalm-6 and the multipotential UT-7, attached to untreated primary stroma and to the human BM stromal cell line Str-5 preferentially using VLA-4. However, treatment of the stroma with TGF-beta1 resulted in a significant reduction in the participation of VLA-4 in mediating precursor cell adhesion to stroma and a concomitant increase in the utilization of VLA-5. This effect was not exclusive of normal BM stroma. Treatment with TGF-beta1 of stroma from multiple myeloma BM samples produced a substantial increase in VLA-5 use by the myeloma cell line NCI-H929 to adhere to this stroma. The differential use of VLA-4 and VLA-5 correlated with an increase in fibronectin surface expression by stromal cells in response to TGF-beta1. Adhesion assays to purified fibronectin using Nalm-6 cells showed a predominant utilization of VLA-4 at low concentrations of this ligand, whereas higher concentrations resulted in a preferential use of VLA-5. These results indicate that regulation of fibronectin expression on BM stromal cells by TGF-beta1 results in a modulation of the pattern of integrins used by the precursor and myeloma cells to adhere to BM stroma, which could have important consequences on the proliferation and differentiation of hematopoietic precursor cells as well as on the localization and growth of myeloma cells.

Bone Marrow Cells↗
PubMed1998

Comparison of the effects of calmidazolium, morphine and bupivacaine on N-methyl-D-aspartate- and septide-induced nociceptive behaviour.

We have recently shown that spinal calmodulin inhibitors (W-7 and calmidazolium) dose-dependently inhibit the nociceptive reaction (biting, scratching, licking, BSL) evoked by intrathecal N-methyl-D-aspartate (NMDA) and septide, an agonist of the neurokinin (NK) NK1 receptor. To compare this effect with that induced by standard analgesics, we now report a study of the effects of calmidazolium (14420 nmol), bupivacaine (29-582 nmol) and morphine (26-260 nmol) when coadministered intrathecally with either NMDA (4 microg) or septide (0.5 microg). Calmidazolium had the highest potency for inhibiting septide-induced nociceptive behaviour, acting over a dose range of 34-130 nmol (dose eliciting a half-maximal response, ED50, 67 nmol) lower than that of bupivacaine [ED50 234 (115-475) nmol]. Only the highest dose of morphine (260 nmol) inhibited septide-evoked BSL [ED50=133 (69-255) nmol]. Higher doses of morphine could not be tested due to the appearance of an excitatory aversive reaction. Both calmidazolium [ED50=232 (138-388) nmol] and bupivacaine [ED50=123 (59-256) nmol] dose-dependently reduced NMDA-induced BSL reaching an almost maximal inhibition at the highest doses assayed (420 and 291 nmol, respectively). In contrast, morphine had less effect on NMDA-induced behaviour, inducing only a partial reduction of BSL even with the highest dose assayed (260 nmol). Overall, it can be concluded that the calmodulin inhibitor calmidazolium inhibits septide- and NMDA-evoked nociceptive behaviour with a potency and efficacy at least as high as those of morphine and bupivacaine.

Analgesics↗
PubMed1998

Partial contribution of polyamines to the relaxant effect of 17 alpha-estradiol in rat uterine smooth muscle.

1. The effects of 17 alpha-estradiol on KCl (60 mM), CaCl2 (30 microM to 10 mM) and vanadate (0.3 mM)-induced contractions in rat uterus have been assayed. Furthermore, the effect of 17 alpha-estradiol on calmodulin-stimulated cAMP-phosphodiesterase activity was also studied. 2. 17 alpha-estradiol relaxed the tonic contraction induced by KCl (60 mM) in a concentration-dependent way (IC50, 8.3 +/- 0.7 microM), and CaCl2 (0.1 to 10 mM) counteracted it. 3. CaCl2 (30 microM to 10 mM) produced concentration-dependent contraction of rat uterus in a calcium-free medium supplemented with 60 mM of KCl (EC50: 0.2 +/- 0.01 mM). 17 alpha-estradiol (8 microM) antagonized the contraction induced by CaCl2, increasing the EC50 value up to 0.7 +/- 0.1 mM (P < 0.01). 4. 17 alpha-estradiol (0.1 to 1 mM) relaxed in a concentration-dependent way the tonic contraction induced by vanadate in rat uterus incubated in a calcium-free medium and EDTA supplemented. The maximal relaxation achieved with 1 mM of 17 alpha-estradiol was 52.2 +/- 2.8%. 5. 17 alpha-estradiol (1 to 100 microM) did not modify the basal activity of cAMP-phosphodiesterase but inhibited the calcium plus calmodulin stimulated activity. The maximal inhibition achieved was 43 +/- 5.4%. 6. The relaxing effect of 17 alpha-estradiol on KCl (60 mM)-induced tonic contraction was unmodified with the antioestrogen tamoxifen (0.1 and 1 microM), the inhibitor of tirosine kinase (genistein, 10 microM) and the cAMP-dependent protein kinase inhibitor (Rp-adenosine 3',5'-monophosphothioate, triethylamine salt, 100 microM). However, the effect was antagonized with the inhibitor of transcription (actinomycin D, 5 micrograms/ml,), the inhibitor of protein synthesis (cycloheximide, 10 and 100 micrograms/ml), and the inhibitor of ornithine decarboxilase (alpha-difluoromethyl-ornithine, 10 mM). 7. Our results suggest that polyamines contribute to the relaxant effect of 17 alpha-estradiol in rat uterine smooth muscle behaving, presumably, as mediators of the transcriptional component involved in the effect of 17 alpha-estradiol.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Nitric oxide and cyclic nucleotides participate in the relaxation of diclofenac on rat uterine smooth muscle.

1. The effect of diclofenac (10-100 microM) on vanadate-induced contraction of rat uterus in calcium-free buffer containing EDTA and the modification of this response by pertussis toxin (50 micrograms/ml), Rp-cAMPS (10 microM), W-7 (10 and 60 microM), L-NMMA (10 and 100 microM) and D-NMMA (100 microM) has been assessed. The effects of sodium nitroprusside (10 microM-1 mM), 3-morpholinosydnonimine (SIN-1; 0.1-100 microM), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ; 0.1-100 microM) and 8-BrcGMP (10 microM to 1 mM) on vandate-evoked contraction were also studied. 2. Diclofenac produced dose-dependent relaxation of vanadate (0.3 mM)-induced contraction (EC50:17.3 +/- 1.8 microM, n = 11). This effect was significantly (P < 0.05) reduced by pertussis toxin (EC50: 37.4 +/- 4.5 microM, n = 6) and Rp-cAMPS (EC50:36.3 +/- 3.1 microM, n = 6). 3. The calmodulin inhibitor W-7 (1-100 microM) relaxed, in a concentration-dependent way, the vanadate contraction (EC50:67.0 +/- 18 microM). W-7 (10 and 60 microM) did not modify the relaxation elicited by diclofenac, which suggests that calmodulin inhibition and the increase of cAMP are two different actions of diclofenac. 4. The action of diclofenac was antagonized (P < 0.05) by L-NMMA (100 microM) and ODQ (1 and 100 microM) but not by D-NMMA (100 microM), which suggests the involvement of NO-synthase in this effect. 5. Sodium nitroprusside (1 mM) relaxed the vanadate contraction by only 31.7 +/- 1.04% (n = 7) and SIN-1 by 27.1 +/- 1.2% (n = 6). This suggests that, under the present experimental conditions, both NO donors were ineffective. However, 8-BrcGMP (EC50:327 +/- 71 microM, n = 7) relaxed this contraction up to 58.7 +/- 1.89%. Rp-cAMPS (10 microM) did not modify the 8-BrcGMP effect. Thus, a partial contribution of cGMP to inhibitor effect of drugs on rat uterus was possible. 6. The association between L-NMMA plus ODQ, L-NMMA plus Rp-cAMPS and ODQ plus Rp-cAMPS did not produce more displacement than L-NMMA, Rp-cAMPS or ODQ alone. This suggests the involvement of NO and cyclic nucleotides in the relaxant effect of diclofenac in rat uterus.

Adenylyl Cyclases↗
PubMed1998

Different types of steroids inhibit [3H]diprenorphine binding in mouse brain membranes.

1. The binding of 60 drugs, mainly steroids, to opioid receptors was studied in crude membrane fractions from mouse brains. 2. Competition assays with the different drugs (5 x 10(-7)-10(-4)M) were performed by labeling opiate receptors with [3H]diprenorphine (0.3-0.4 nM). 3. Only 7 drugs (alpha,5beta-tetrahydrodeoxycorticosterone, megestrol acetate, mifepristone, 17alpha-ethynylestradiol, diethylstilbestrol, clomiphene citrate and tamoxifen citrate) inhibited [3H]diprenorphine binding more than 50% at the highest concentration assayed (10(-4) M). The IC50 values ranged between 6x10(-5) M. 4. Thus, the present results show that only a limited number of steroids, from diverse classes, bind to opiate receptors.

Animals↗