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Biomedical subjects

J D Martín

Publications and source records attributed to J D Martín.

At least 19 recordsLinked to original sources
PubMed2005

Supramolecular aggregation of two hydroxycarboxylic acid derivatives.

The crystal structures of 7,7-dicyclobutyl-5-hydroxymethyl-6-oxabicyclo[3.2.1]octane-1-carboxylic acid, C17H26O4, (I), and 1-(hydroxymethyl)-7-oxaspiro[bicyclo[3.2.1]octane-6,1'-cyclopentane]-5-carboxylic acid, C13H20O4, (II), determined at 170 K, show that the conformation of the hydroxymethyl group (anti or gauche) affects the dimensionality (one- or two-dimensional) of the supramolecular structures via O-H...O hydrogen bonds. In (I), the carboxyl and hydroxymethyl groups interact with themselves, forming a one-dimensional step-ladder, while in (II), a two-dimensional structure is made up of carboxylic acid centrosymmetric R(2)2(8) dimers connected by hydroxyl-to-ether contacts.

Journal Article↗
PubMed2005

Hydrogen-bonding patterns of two dihydroxylactone derivatives.

In the hydrogen-bonding networks of 8-hydroxy-5-hydroxymethyl-3,6-dioxatricyclo[6.3.1.0(1.5)]dodecan-2-one and 5,7-bis(hydroxymethyl)-3,6-dioxatricyclo[5.3.1.0(1.5)]undecan-2-one, both C11H16O5, layers and double strands, respectively, lead to the formation of chains connected by hydroxy-to-hydroxy contacts, where the hydroxymethyl group, present in both structures, acts as a donor. The secondary structures differ in the hydrogen bonding of these chains via the second hydroxy group, which is involved in hydroxy-to-carbonyl and hydroxy-to-hydroxy bonds, respectively.

Journal Article↗
PubMed2004

Tachykinins and tachykinin receptors: structure and activity relationships.

In addition to the classical neurotransmitters, acetylcholine and noradrenaline, a wide number of peptides with neurotransmitter activity have been identified in the past few years. Among them, the tachykinins substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) appear to act as mediators of nonadrenergic, noncholinergic (NANC) excitatory neurotransmission. Tachykinins interact with specific membrane proteins, belonging to the family of G protein-coupling cell membrane receptors. Until now, three tachykinin receptors termed NK1 (NK1R), NK2 (NK2R) and NK3 (NK3R) have been cloned in different species. A large amount of reports suggests that these peptides are involved in nociception and neuroimmunomodulation, and in the development of different diseases such as bronchial asthma, inflammatory bowel syndrome and psychiatric disorders. Tachykinin receptor antagonists are therefore promising, therapeutically relevant agents. However, and in spite of extensive research, the obtention of selective antagonists of tachykinin receptors have revealed very difficult. An understanding of how ligands interact with their receptors is essential to permit a rational design of compounds acting selectively at the tachykinin receptor level. The major aim of the present article is to review the structure-activity data that exist for tachykinins and their receptors, with the purpose of getting insight into basic structural requirements that determine ligand/receptor interaction.

Amino Acid Sequence↗
PubMed2001

Tubular hydrogen-bonded networks sustained by water molecules.

The design concept of functional solids relies on controlling the topology of crystal packing through exploitation of weak intermolecular forces. In the context of cyclic aggregates, the ability to anticipate the consequences of ring constituents and their stereochemistries on ring conformation is vitally important since even an apparently slight structural change effected on molecules can dramatically alter the crystal structure. We have found that solid-state structures formed by hydroxy acids with a general structure (+/-)-1 depend on steric interactions. Thus, with the exception of molecules 1b and 1e, compounds (+/-)-1a-(+/-)-1m, which possess bulky and conformationally rigid substituents, aggregate by forming tapes and sheets by alternating (+) and (-) subunits held together through carboxylic acid-to-alcohol hydrogen bonds. Homologue (+/-)-1n, with conformationally flexible substituents which allow conformational deformation, gives, by incorporation of molecules of water, an efficient hexagonal assembly which extends to the third dimension to form tubular H-bonding networks. Each puckered channel can be described as interconnected closely packed hexagons in chairlike conformations. The ethyl groups presented in (+/-)-1n gave the volume required to lock the inner hexagonal wall into a rigid structure. Attempts to obtain cyclic aggregates using small substituents, compounds (+/-)-1o-(+/-)-1q, failed. The observed supramolecular assemblies of the anhydrous compounds can be classified into one-dimensional strands and two-dimensional sheets, while three-dimensional networks are present only in the hydrated molecules (1b, 1e, and 1n). The crystal structure of the anhydrous (+/-)-1n compound confirms the important role played by water molecules in the formation of tubular structures.

Journal Article↗
PubMed2001

Changes in the expression of tachykinin receptors in the rat uterus during the course of pregnancy.

In the mammalian female reproductive tract, tachykinin neuropeptides, such as substance P (SP), are localized to a population of sensory fibers and their precise physiological role is still unknown. The aim of the present study was to characterize the population of tachykinin receptors in the pregnant rat uterus and to assess their regulation during the course of pregnancy and after delivery. The expression of the tachykinin NK(1) receptor (NK(1)R), the tachykinin NK(2) receptor (NK(2)R), and the tachykinin NK(3) receptor (NK(3)R) in uteri from rats at different stages of pregnancy and on Day 1 postpartum was investigated by using a semiquantitative reverse transcription-polymerase chain reaction. The contractile effect of tachykinin receptor agonists acting selectively on the NK(1)R, the NK(2)R, or the NK(3)R was investigated by conventional organ bath techniques. Serum levels of estrogen and progesterone were measured by RIA. Our data show that the expression and function of NK(1)R and NK(3)R varied along the course of pregnancy and at postpartum. Uterine NK(2)R mRNA levels remain stable during the course of pregnancy and at Day 1 postpartum; and the contractions elicited by activating selectively the NK(2) receptor in the presence of the neutral endopeptidase inhibitor phosphoramidon (1 microM) were similar in early, mid, or late pregnancy. These results show that the expression and function of tachykinin receptors within the uterus vary with reproductive state and length of gestation, supporting a role for tachykinins in pregnancy and/or parturition in the rat.

Animals↗
PubMed2001

Hormonal regulation of the contractile response induced by okadaic acid in the rat uterus.

The contractile effect of okadaic acid (OA), a highly selective inhibitor of protein serine/threonine phosphatases, was analyzed in the rat uterus during the estrous cycle and during the course of pregnancy. Contractile effects were related to circulating levels of estrogen and progesterone and to mRNA levels of myosin light chain kinase (MLCK) and of myosin light chain protein phosphatase catalytic (PP1-delta) and larger regulatory subunit (MYPT). Both in nonpregnant and pregnant uteri, OA (20 microM) induced a transient contraction, which after plateauing, slowly decreased. In the nonpregnant uterus, the amplitude of this contraction varied at different stages of the estrous cycle, being higher at proestrus and lower at diestrus. In the pregnant uterus, the contraction to OA increased significantly during the course of pregnancy, reaching a maximum in day 21 pregnant rats, and declined after delivery. Whatever the day of pregnancy, the amplitude of the contraction to OA was not significantly modified when obtained in Ca(2+)-free solution. The magnitude of the OA-induced contraction in spontaneously cycling and pregnant rats was positively correlated to the ratio of estrogen/progesterone serum levels. Reverse transcription-polymerase chain reaction assays on myometrial tissue demonstrated that mRNA expression of PP1-delta and MYPT was higher at early (day 3) than at late (day 21) pregnancy. MLCK mRNA levels were similar in day 3 and day 21 pregnant rats. These data suggest that changes in the expression and activity of myosin phosphatase may contribute to modulating the level of uterine contractile force during the estrous cycle, pregnancy, and labor.

Animals↗
PubMed1999

Synthesis of novel polyethers in a geometrically precise conformation.

[reaction: see text] A convergent design for the preparation of a polyoxyethylene-based channel molecule is presented, and the synthesis of the key unit 2 required for the projected construction is described. The essential elements of the design included face to face oriented macrorings spaced by rigid trans-fused oxanes. The strategy combines conformational predictability of C-linked oxanyl systems and ring-closing metathesis for the synthesis of crown ethers with engineerable ion-binding abilities.

Journal Article↗
PubMed1999

Tachykinin receptor and neutral endopeptidase gene expression in the rat uterus: characterization and regulation in response to ovarian steroid treatment.

Tachykinin neuropeptides, such as substance P, are localized to a population of sensory fibers that innervate the mammalian female reproductive tract. In the present study, we have characterized tachykinin NK1 receptor (NK1R), NK2 receptor (NK2R), and NK3 receptor (NK3R) gene expression by semiquantitative RT-PCR in uteri from ovariectomized rats and studied their regulation in response to 17beta-estradiol (E2), progesterone (P4), or a combination of both. In addition, we analyzed the expression and regulation of the neutral endopeptidase 24.11 (NEP), the most important enzyme involved in tachykinin degradation in the rat uterus. In uteri from control (olive oil-treated) rats, RT-PCR assays revealed single bands corresponding to the expected product sizes encoding complementary DNA for NK1R (232 bp), NK2R (491 bp), NK3R (325 bp), and NEP (221 bp). The identity of the amplified fragments was confirmed by DNA sequence analysis. Compared with control rats, NK1R messenger RNA (mRNA) was increased by 2-fold in uteri from rats treated with E2, was decreased by 3.3-fold in rats treated with P4, and was decreased by 1.8-fold in rats treated with both E2 and P4. Uterine NK2R mRNA levels were not altered by any steroid treatment. E2 treatment decreased by 15-fold NK3R mRNA. P4 was without effect if administered alone and did not influence the E2-induced decrease in NK3R mRNA. NEP mRNA levels were about 4-fold lower in E2-treated than in P4-treated rats. Functional studies were carried out in uteri from E2- or P4-treated ovariectomized rats to characterize the contractile response evoked by the selective tachykinin receptor agonists [Sar9Met(O2)11]substance P (NK1R selective), [Nle10]NKA-(4-10) (NK2R selective), and [MePhe7]NKB (NK3R selective) in the presence of the NEP inhibitor phosphoramidon (1 microM). A marked correlation was observed between the magnitude of the contractile response to each agonist and the level of expression determined by RT-PCR for each tachykinin receptor. The present findings show that tachykinin NK1R, NK2R, NK3R, and NEP are expressed in the rat uterus and that ovarian steroids differentially regulate their expression.

Animals↗
PubMed1998

Characterization of tachykinin receptors in the uterus of the oestrogen-primed rat.

1 The aim of our study was to characterize the tachykinin receptor population in the oestrogen-primed rat uterus. For this purpose, we investigated the receptor type(s) responsible for tachykinin-induced contraction of longitudinally-arranged smooth muscle layer. The effects of substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and several of their analogues with well-defined selectivities for tachykinin NK1, NK2 and NK3 receptors were studied and their inhibition by the selective nonpeptide tachykinin receptor antagonists (S)1-(2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)pip eridin-3-yl]ethyl)-4-phenyl- -azoniabicyclo[2.2.2]octane chloride (SR 140333, NK1-selective), (S)-N-methyl-N[4-(4acetylamino-4-phenylpiperidino)-2-(3,4-dichloro phenyl)butyl]benzamide (SR 48968, NK2-selective) and (R)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)prop yl)-4-phenylpiperidin-4-yl)-N- methyla-cetamide (SR 142801, NK3-selective) was evaluated. Additionally, expression of tachykinin receptor mRNA was examined by using the reverse transcription-polymerase chain reaction (RT-PCR). 2 SP, NKA, [Nle10]-NKA(4-10), the analogue with selectivity at the tachykinin NK2 receptor type, and NKB elicited concentration-dependent contractions of the rat uterus. The pD2 values were 5.95+/-0.19; 6.73+/-0.21; 7.53+/-0.12 and 5.76+/-0.21, respectively. The selective agonist for the tachykinin NK1 receptor [Sar9Met(O2)11]-SP produced a small phasic response in the nanomolar concentration range. The selective tachykinin NK3 receptor agonist [MePhe7]-NKB failed to induce any significant contraction. 3 In the presence of the neutral endopeptidase inhibitor phosphoramidon (1 microM), the log concentration-response curves to exogenous tachykinins and their analogues were shifted significantly leftwards. The pD2 values were 6.12+/-0.10, 8.04+/-0.07, 7.89+/-0.03 and 6.59+/-0.07 for SP, NKA, [Nle10]-NKA(4-10) and NKB, respectively. In the presence of phosphoramidon (1 microM), [Sar9Met(O2)11]-SP (1 nM - 0.3 microM) induced concentration-dependent contractions of increasing amplitude when only one concentration of drug was applied to each uterine strip and the pD2 value was 7.61+/-0.89. [MePhe7]-NKB induced small, inconsistent contractions and, therefore, a pD2 value could not be calculated. 4 In experiments performed in the presence of phosphoramidon (1 microM), SR 48968 (3 nM - 0.1 microM) caused parallel and rightward shifts in the log concentration-response curves of NKA. The calculated pKB value was 9.16+/-0.08 and the slope of the Schild regression was 1.28+/-0.24. SR 48968 (0.1 microM) also antagonized responses to SP with an apparent pKB value of 7.63+/-0.13. SR 48968 (0.1 microM) inhibited contractions elicited by NKB (1 nM - 3 microM) and [Nle10]-NKA(4-10) (0.1 nM - 3 microM) but had no effect on the response evoked by [Sar9Met(O2)11]-SP (0.1 microM). 5 SR 140333 (0.1 microM) inhibited responses to SP with an apparent pKB value of 7.19+/-0.22. This compound did not significantly affect responses to NKA, [Nle10]-NKA(4-10) and NKB, but suppressed [Sar9Met(O2)11]-SP (0.1 microM)-induced contraction. SR 142801 (0.1 microM) had no effect on responses to natural tachykinins or their analogues. 6 Total RNA was extracted from some of the uteri used in functional studies. RT-PCR assays revealed single bands corresponding to the expected product sizes encoding cDNA for tachykinin NK1 (587 base pairs) and NK2 receptors (491 base pairs) (n=6 different animals). A very low abundance transcript corresponding to the 325 base pairs product expected for the tachykinin NK3 receptor was detected. 7 The present data show that functionally active tachykinin NK1 and NK2 receptors are expressed in the oestrogen-primed rat uterus. The NK2 receptor type seems to be the most important one involved in the contractile responses elicited by tachykinins. NK3 receptors are present in trace amounts and seem not to be involved in tachykinin-induced contractions.

Animals↗
PubMed1997

Effects of Mn2+ on the responses induced by different spasmogens in the oestrogen-primed rat uterus.

We investigated the effect of Mn2+ on the mechanical responses evoked by high K+ (60 mM) or low Na+ (25 mM) solutions, oxytocin and neurokinin A in the oestrogen-primed rat uterus. In a Ca2+-free, Mn2+ (0.54 mM)-containing solution, high K+ or low Na+ solutions produced contractions of smaller amplitude than those observed in a normal Ca2+ (0.54 mM) solution, which were abolished by nifedipine (1 microM). Oxytocin (1 microM) and neurokinin A (1 microM, in the presence of phosphoramidon 1 microM) evoked nifedipine-insensitive contractile responses similar to (oxytocin) or smaller (neurokinin A) in amplitude than those observed in Ca2+ (0.54 mM)-containing solution. In strips loaded with Ca2+ (2.16 mM) for 10 min and then exposed to a Ca2+- and Mn2+-free, EGTA (3 mM)-containing medium for 4 min, both oxytocin and neurokinin A induced transient contraction followed by a small sustained response. The transient component of the response was abolished by cyclopiazonic acid (10 microM). When preparations were loaded with Mn2+ (2.16 mM) for 10 min, only the small, tonic contraction was observed. In Ca2+-containing solution, Mn2+ (0.01-10 mM) inhibited in a concentration-dependent manner the rhythmic contractions developed either spontaneously or by electrical stimulation as well as high K+- and neurokinin A-induced contractions. Mn2+ also abolished the rhythmic, but not the tonic component of the response to oxytocin, and the preparation remained maximally contracted. These data suggest that in the oestrogen-primed rat uterus, Mn2+ acts as an antagonist of Ca2+ influx through L-type voltage-operated Ca2+ channels. In addition, Mn2+ enters the cell mainly through nifedipine-insensitive receptor-operated channels and, to a lesser degree, through L-type Ca2+ channels to produce contraction by directly activating the contractile machinery.

Animals↗
PubMed1997

Regulation by oestrogens of tachykinin NK3 receptor expression in the rat uterus.

The expression of the tachykinin NK3 receptor and its regulation by ovarian steroids were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) in uteri from ovariectomized rats. A single transcript corresponding to the 325-bp product expected for the tachykinin NK3 receptor was detected in uteri from olive oil-treated (control) ovariectomized rats. The level of tachykinin NK3 receptor mRNA in progesterone-treated animals was similar to that observed in uteri from control ones. Tachykinin NK3 receptor mRNA levels were significantly smaller in uteri from oestrogen-treated ovariectomized rats, with approximately a 32-fold decrease. These findings suggest that oestrogen, but not progesterone, regulates the expression of tachykinin NK3 receptors in the rat uterus.

Animals↗
PubMed1997

Inhibitory effects of okadaic acid on rat uterine contractile responses to different spasmogens.

In the present study, we examined the effects of okadaic acid, a selective inhibitor of type 1 and 2A protein phosphatases, on the mechanical responses evoked by oxytocin, K(+)- and Na(+)-modified solutions and ouabain in estrogen-primed rat myometrium. Oxytocin elicited a rapid, phasic contraction followed by rhythmic oscillations. The phasic response was partially resistant to the absence of external Ca2+. Okadaic acid (1 microM) and the L-type calcium channel blocker nifedipine (1 microM) abolished the oscillatory component and reduced the initial, phasic response to about 80% of the control response. High K+ (60 mM) solution, ouabain (1 mM), K(+)-free medium and low Na+ (25 mM) solution induced extracellular Ca(2+)-dependent biphasic responses composed by an early rapid (KCl, ouabain and K(+)-free solution) or slower developed (25 mM Na+ solution) phasic contraction followed by a sustained increase in tension. Okadaic acid and nifedipine, alone or in combination, abolished or decreased similarly the contractile response evoked by these stimulants. The okadaic acid- and nifedipine-insensitive responses to ouabain, K(+)-free and low Na+ solution were enhanced by increasing the extracellular concentration of Ca2+ in the medium and were inhibited in a dose-dependent manner by amiloride (0.05-0.5 mM). These data suggest that, in estrogen-primed rat uterus, dephosphorylating mechanisms by OA-sensitive protein phosphatases play an important role in regulating myometrial contractions elicited by Ca2+ entry through voltage-sensitive Ca2+ channels.

Animals↗
PubMed1997

An analysis of the mechanisms involved in the okadaic acid-induced contraction of the estrogen-primed rat uterus.

The contractile effect of okadaic acid (OA) and its derivatives was investigated in the rat uterus. OA (20 microM) induced a transient contraction which, after plateauing, slowly decreased. The structurally related compound okadanol (20 microM) failed to induce any significant contraction. Conversely, the synthetic compound methyl okadaate (20 microM) and the naturally occurring ester 7'-hydroxy-4'-methyl-2'-methylen-hept-4'(E)-enyl okadaate (20 microM) were as active as the free acid. The OA-induced contraction was unaffected in the presence of neomycin (5 mM), mepacrine (30 microM), 1-[N,O-bis(1,5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperaz ine (10 microM), calphostin C (3 microM) and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (30 microM). The calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (100 microM) did not modify the amplitude of the OA-induced contraction but significantly increased the rate of tension decay. The myosin light chain kinase inhibitor 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (1 mM) significantly reduced the peak amplitude of the contraction. Staurosporine (0.03-0.1 microM) did not modify the contractile component of the OA-induced response but inhibited the subsequent decrease in tension. In freshly dispersed myometral cells loaded with the fluorescent Ca++ indicator indo 1, OA did not produce any significant increase in [Ca++]i. OA (5- to 90-min contact) also failed to modify the intracellular levels of arachidonic acid, compared with basal values. These data suggest that in the rat uterus 1) the contractile effect of OA (20 microM) is specifically mediated by inhibition of protein phosphatases type 1 and/or 2A and is related to a direct interaction with the contractile machinery; 2) the decreasing phase of the OA-induced mechanical response could be mediated by a staurosporine-sensitive protein kinase different from protein kinase C.

Animals↗
PubMed1996

Effect of inhibition of the electrogenic Na+/K+ pump on the mechanical activity in the rat uterus.

The effects of ouabain and K(+)-free solution were studied in estrogen-primed rat uterine strips under resting tone or repeatedly stimulated with KCl, acetylcholine or oxytocin applied for 20 minutes at 60 minute intervals. These effects were compared with those of the K+ channel opener cromakalim. In preparations under resting tone, ouabain (0.1 mM and 0.3 mM) induced rhythmic contractions which disappeared after 20-30 minutes whereas at a higher concentration (1 mM) it evoked a rapid, phasic response followed by a small tonic contraction. Exposure of the strip to a K(+)-free solution induced either rhythmic waves, which ceased after 8-10 minutes, or a single phasic contraction which was followed by a small and slow increase in the resting tone (54 +/- 10 mg after 180 min exposure). Nifedipine (0.3 microM) abolished the rhythmic or phasic component of these responses but failed to modify the late small tonic contraction induced by ouabain 1 mM or by K(+)-free solution. Ouabain (0.1-1 mM) or K(+)-free-evoked responses disappeared after short (4 min) or prolonged (60 min) exposure to a Ca(2+)-free, 3 mM EGTA-containing solution. Cromakalim (10 nM-0.1 mM) did not induce any variation in the resting tone either in the presence or in the absence of Ca2+ in the medium. In strips repeatedly stimulated with acetylcholine (0.1 mM) or oxytocin (1 microM), ouabain (0.3 mM), K(+)-free-solution and cromakalim (10 microM) reduced the amplitude of the initial, phasic response and progressively decreased the oscillatory component of the response to these agonists. Conversely, the successive responses evoked by KCl 60 mM in similar experimental conditions were not affected by ouabain or cromakalim. Ouabain (0.3 mM), K(+)-free solution and cromakalim (10 microM) decreased the Ca(2+)-independent, maintained contractions induced by acetylcholine or oxytocin after prolonged exposure to a Ca(2+)-free, EGTA-containing medium. These inhibitory effects were partially or completely reversed in the presence of the non-selective potassium channel blocker tetraethylammonium (10 mM) or in a Ca(2+)-free solution containing 60 mM K+. In conclusion, these results suggest that the response induced by ouabain or K(+)-free solution in estrogen-primed rat myometrium involves Ca2+ influx through potential-operated calcium channels but not Ca2+ release from intracellular stores. In addition, our results show that prolonged exposure to ouabain or K(+)-free medium decreases membrane receptor-mediated responses in rat uterus. This inhibitory effect seems to be the result, at least in part, of a decrease in the cytosolic level of K+, due to the inhibition of the electrogenic Na+ pump.

Acetylcholine↗
PubMed1994

Influence of calcium on the effects of okadaic acid and its interaction with caffeine and theophylline in rat myometrium.

The effects of okadaic acid (OA), a monocarboxylic acid produced by marine dinoflagellates belonging to the genera Dinophysis and Prorocentrum, and their interactions with theophylline and caffeine were studied on the rat-isolated uterus in a calcium-containing medium and a calcium-free medium in the presence of 10(-3) M EGTA. Okadaic acid (5 x 10(-6) to 5 x 10(-5) M) induced a concentration-dependent contraction of the rat-isolated uterus corresponding, with 5 x 10(-5) M, to 142.3 +/- 6.1% (n = 7) of the contraction induced by oxytocin 10(-6) M. The time to peak tension was inversely proportional to the maximum effect produced. The contraction was not sustained and was followed by a concentration-dependent decrease in tone. In a Ca(2+)-free medium containing 10(-3) M EGTA the contractile effects of OA were significantly inhibited or reduced. A 30 min pretreatment with theophylline (3 x 10(-3) M) or caffeine (2 x 10(-2) M) significantly reduced, in a Ca(2+)-containing medium, the maximum contractile effect of OA 10(-5) and/or 2 x 10(-5) M and shortened the relative time to peak tension. In a Ca(2+)-free medium containing 10(-3) M EGTA, only the second effect was observed. With a 1 min pretreatment and in a Ca(2+)-containing medium, theophylline 3 x 10(-3) M and caffeine 10(-2) M did not modify the maximum effect of OA 10(-5) M but shortened the time to peak tension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Inhibitory and contractile effects of okadaic acid on rat uterine muscle.

The effects of okadaic acid and its interactions with various agents known to increase, by different mechanisms, the intracellular levels of cyclic AMP and/or cyclic GMP were investigated in isolated strips of rat myometrium. Okadaic acid showed inhibitory effects at concentrations between 10(-7) M and 3 x 10(-6) M. At higher concentrations, a biphasic, contractile and then relaxant response was observed. The results obtained suggest that, in rat uterine smooth muscle, the inhibitory effects of okadaic acid are not entirely mediated by the activation of cyclic AMP- and/or cyclic GMP-dependent pathways. The data also point to the existence of a clear interaction between okadaic acid and methylxanthines, although further studies are needed to clarify the mechanisms involved in this interaction.

Animals↗
PubMed1989

Muscle regeneration induced by snake venom. A histological and histochemical study.

This report describes the regeneration pattern of anterior tibial muscle of the rat after the inoculation of the snake venom of Bothrops jararacussu. The results show that this regeneration pattern is rather similar to the pattern described in other experimental models. Three days after the injection, three differentiated areas are established: a peripheric one of surviving fibres, a second one called myogenic area, and the last one, more internal, made of necrotic fibres that are phagocytized by macrophages. The surface of the surviving muscle fibres has myoblasts sticking to it and five days after, the myogenic area is occupied by many of them. Both the previous phagocytosis and the myoblasts came from the area of current uninjured fibres. After 30 and 60 days the regeneration is completed and there are only a few marks that show that the regeneration has taken place.

Acid Phosphatase↗