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Biomedical subjects

A Meli

Publications and source records attributed to A Meli.

At least 199 records · Page 11Linked to original sources
PubMed1985

Dual effect of GABA on the contractile activity of the guinea-pig isolated urinary bladder.

The effects of GABA and related substances were examined in isolated detrusor strips from the dome of the guinea-pig urinary bladder. GABA (0.01-1 mM) produced concentration-related phasic contractions of isolated strips from the guinea-pig urinary bladder dome. This effect of GABA was mimicked by homotaurine and muscimol, selective GABAA receptor agonists but not by (+/-)-baclofen, a selective GABAB receptor agonist. A specific cross desensitization was observed between GABA, homotaurine and muscimol but not between (+/-)-baclofen and GABA. GABA (1 mM)-induced contractions were antagonized by picrotoxin, a selective GABAA receptor antagonist. GABA-induced contractions were almost abolished by tetrodotoxin (0.5 microM, TTX) thus indicating their neurogenic origin. In addition GABA-induced contractions were partially antagonized by atropine (to about the same extent as those produced by dimethylphenylpiperazinium (DMPP), a ganglionic stimulant), but were unaffected by hexamethonium (10 microM), phentolamine (0.2 microM) or indomethacin (5 microM). In the presence of GABA the contractile effect of both DMPP (TTX-sensitive) and acetylcholine (ACh, TTX-insensitive) were significantly reduced. Similar findings were obtained with DMPP, i.e. in preparations exposed to this ganglionic stimulant both GABA- and ACh-induced contractions were depressed. Homotaurine but not (+/-)-baclofen mimicked the depressant effect of GABA on DMPP-induced contractions. The depressant effect of GABA on ACh-induced contractions of the guinea-pig urinary bladder was neurogenic in origin, i.e., was not observed in preparations exposed to TTX. These experiments indicate that GABA has a dual effect on the contractile behaviour of the guinea-pig isolated urinary bladder. Recently it has been proposed that endogenous GABA plays a neuromodulatory role in this organ. Our data suggest that in the early phase of neurogenic activation of detrusor muscle (micturition reflex) GABA might transiently enhance excitatory neurotransmission followed by a more sustained inhibition of contractility.

Acetylcholine↗
PubMed1985

Contribution of neurogenic and myogenic factors to the contractile activity of the guinea-pig distal colon in vivo and in vitro.

The response of the guinea-pig distal colon to distension and drugs expected to interfere with neural control of contractile activity were investigated in urethane anaesthetized animals and compared to results obtained in the isolated preparation. Under urethane anaesthesia bout 50% of the unloaded preparations had no detectable contractile activity. However these preparations contracted in response to topical acetylcholine. Saline distension induced the appearance of a phasic contractile activity in 'quiescent' preparations and enhanced amplitude of contractions in previously active ones. Atropine (1 mg/kg i.v.) reduced tone and transiently suppressed phasic contractile activity of the distal colon. When phasic contractile activity resumed a second dose of atropine had no further inhibitory effect. Topical physostigmine (20 micrograms in 0.1 ml) produced a marked and long lasting increase in tone paralleled by a marked enhancement in amplitude of the phasic contractile activity. These excitatory effects of topical physostigmine were suppressed by intravenous atropine (1 mg/kg). Hexamethonium (20 mg/kg i.v.) produced a sudden and transient increase in tone and suppressed DMPP (0.1 mg/kg i.v.) but not noradrenaline (2 micrograms/kg i.v.) induced relaxations. Propranolol (2 mg/kg i.v.) or phentolamine (0.5 mg/kg i.v.) transiently increased tone of the guinea-pig distal colon and suppressed noradrenaline induced relaxations. DMPP induced relaxations were reduced by propranolol plus phentolamine. Topical tetrodotoxin (50 micrograms in 0.1 ml) had an overall slight excitatory effect on phasic contractile activity of the in vivo preparation. The effects of i.v. atropine, hexamethonium, phentolamine or propranolol on tone and spontaneous activity were prevented by pretreatment with tetrodotoxin. Isolated segments of guinea-pig distal colon exhibited a fairly regular spontaneous phasic contractile activity whose amplitude was increased by stretching of the preparation. Atropine (3 microM) produced a transient inhibition while hexamethonium (40 microM) had no effect on spontaneous contractile activity. Tetrodotoxin (0.5 microM) had both inhibitory and excitatory effects on tone and spontaneous activity of the preparation. At steady state amplitude of contractions was enhanced (15-30% increase) by tetrodotoxin. DMPP (1-100 microM) first induced a phasic contraction and then suppressed transiently the spontaneous activity of the isolated preparation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Pharmacological evidence for the existence of two components in the twitch response to field stimulation of detrusor strips from the rat urinary bladder.

Isolated strips from the anterior dome of the rat urinary bladder respond to single pulse field stimulation with a contraction. Two distinct components of this contraction ("early' and "late') could be observed, both of which were unaffected by hexamethonium (10 microM) and almost abolished by tetrodotoxin (1 microM) indicating their dependence on neurotransmitter release from postganglionic nerve endings. Atropine (3 microM) inhibited the "late' component (over 60%) to a significantly greater extent than the "early' component (less than 10%) Amplitude of the "early' component was usually greater than that of the "late' component. There was almost no difference between the "early' and "late' component in respect of their relationship to stimulus strength and pulse duration. Physostigmine (0.03 microM) enhanced both components of the nerve-mediated contraction, although enhancement of the "late' component was much greater than that of the "early' one. Tetraethylammonium (TEA, 0.5-5 mM) enhanced, in a concentration-related manner, both "early' and "late' components of the nerve-mediated contraction. Following exposure to physostigmine or TEA (5 mM) both "early' and "late' components of contraction were almost completely inhibited by tetrodotoxin. Atropine inhibition was more evident on the "late' as compared to "early' component of contraction. These findings demonstrate the presence, in the twitch response of rat isolated urinary bladder to field stimulation, of two nerve-mediated components which exhibit a different susceptibility to atropine and physostigmine.

Animals↗
PubMed1985

GABAA and GABAB receptors in detrusor strips from guinea-pig bladder dome.

The effects of various GABAA and GABAB receptor agonists and antagonists on electrically induced contractions of detrusor strips from guinea-pig urinary bladder dome were investigated by using both supra and submaximal parameters of stimulation. In supramaximally stimulated preparations GABA (1 mM) inhibited amplitude of contractions. This effect was mimicked, to a lesser degree, by the selective GABAB receptor agonist, (+/-)-baclofen (0.1 mM). Exposure to (+/-)-baclofen reduced markedly the effects of a subsequent challenge with GABA. The GABAA receptor agonists, muscimol (0.3 mM) and homotaurine (1 mM), produced a slight inhibition of contractions and reduced the effects of a subsequent challenge with GABA. The selective GABAA receptor antagonist, picrotoxin (0.1 mM), had a slight, but significant, antagonistic effect toward GABA, but had no effect against (+/-)-baclofen. GABA inhibition of supramaximally stimulated contractions was partly reduced by previous exposure to atropine (3 microM) or to the putative P2-purinoreceptor antagonist, reactive blue 2 (0.3 mM) as well as by desensitization of P2-purinoreceptors produced by the stable ATP analogue beta-gamma-methylene ATP (APPCP). GABA inhibition was unaffected by phentolamine (0.2 microM), propranolol (0.3 microM) or hexamethonium (10 microM). The inhibition produced by atropine plus reactive blue 2 or APPCP desensitization was additive or more than additive. In submaximally stimulated preparations GABA (0.01-1 mM) produced a transient, concentration related enhancement of amplitude of contractions. This effect was mimicked by either muscimol (0.3 mM) or homotaurine (1 mM) but not by (+/-)-baclofen (0.1 mM). A cross desensitization could be observed between the effects of muscimol or homotaurine on one hand and GABA on the other, but not between (+/-)-baclofen and GABA. Picrotoxin (0.03-0.1 mM) produced a concentration dependent antagonism of a noncompetitive type against the excitatory effect of GABA in submaximally stimulated preparations. Previous exposure to either atropine (3 microM), phentolamine (0.2 microM) or hexamethonium (10 microM) failed to affect GABA induced enhancement of submaximally stimulated contractions. On the other hand the effects of GABA were reduced by reactive blue 2 (0.1-0.9 mM) or by desensitization of P2-purinoreceptors. In preparations exposed to tetrodotoxin (TTX, 0.3 microM), field stimulation induced contractions are attributable to a direct excitation of smooth muscle cells. Under these conditions GABA (1 mM) was ineffective, indicating that, in the absence of TTX, it affects the excitability of neural elements in the bladder wall.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Intracisternal glycine activates the micturition reflex in urethane-anaesthetized rats.

Intracisternal glycine, but not GABA, activates a series of neurogenic rhythmic contractions of the urinary bladder in urethane-anaesthetized rats. This effect of glycine was prevented by strychnine but not by bicuculline, indicating the involvement of specific glycinergic receptors. The effects of glycine were also prevented by either atropine or haloperidol suggesting an involvement of cholinergic and monoaminergic excitatory neurotransmission to the bladder.

Anesthesia↗
PubMed1985

GABA inhibits excitatory neurotransmission in rat pelvic ganglia.

Intravenous GABA inhibited, in a bicuculline-sensitive manner, contractions of the urinary bladder induced by preganglionic nerve stimulation in urethane anaesthetized rats, while it had no significant effect on contractions produced by postganglionic nerve stimulation. In addition, intravenous GABA strongly inhibited DMPP-induced bladder contractions; this effect was also prevented by bicuculline. These experiments suggest that GABA inhibits excitatory neurotransmission in rat pelvic ganglia through a mechanism involving, at least in part, the activation of postsynaptic GABA A receptors.

Animals↗
PubMed1985

High-cholesterol diet induces altered responsiveness of rabbit arterial smooth muscle to noradrenaline.

The potential effect of feeding a high-cholesterol atherogenic diet (HCD) on in vitro responsiveness of rabbit arterial smooth muscle was investigated. The vasoconstrictor response produced by either exogenous or endogenous (field stimulation) noradrenaline was significantly depressed in isolated segments of ear artery after HCD as compared to regular diet fed animals. On the other hand no changes to high K+ could be observed in arterial segments after HCD as compared to regular diet fed rabbits. In addition, the alpha-adrenoceptor-mediated inotropic response and contraction of bladder smooth muscle showed only minor or no changes after HCD as compared to regular diet fed rabbits.

Adrenergic alpha-Agonists↗
PubMed1985

Further studies on the mechanism of fat-free diet (FFD)--protection against indomethacin-induced intestinal ulcers in the rat.

A fat-free diet (FFD) reduces bacterial flora when compared to a regular diet (RD) in rats. FFD reduces the degree and incidence of indomethacin-induced intestinal ulceration concomitantly with a reduction in bacterial flora overgrowth produced by the drug. Present and previous findings indicate that diminished deconjugation of indomethacin and reduction of intestinal flora overgrowth play a major role in the ulcer-preventing properties of FFD.

Animals↗
PubMed1985

Regional selectivity of calcium blockers at intestinal level.

Exposure of isolated segments of rat duodenum and proximal colon to either high K+ (55.9 mM) or carbachol (0.1 mM) produced a typical biphasic contraction whose tonic component appears to be almost entirely dependent upon the presence of extracellular Ca++. Verapamil and nifedipine suppressed high K+-and carbachol-induced tonic contractions of both duodenum and proximal colon but a large component of carbachol-induced contraction of proximal colon was insensitive to these substances. Verapamil and nifedipine were: a. 5 and 3 times more effective in antagonizing high K+-induced tonic contractions in the rat duodenum than in the proximal colon, respectively, and b. 10 and 4 times more effective in antagonizing high K+ than carbachol induced tonic contractions of rat duodenum, respectively. The verapamil- or nifedipine- resistant component of carbachol induced tonic contraction of proximal colon was suppressed by drugs which, like octylonium bromide and urethane, have been shown to interfere with mobilization of Ca++ from intracellular storage sites. Experiments in Ca++-free medium indicate the existence in the proximal colon of a significant intracellular Ca++ store which could be mobilized during carbachol but not high K+-induced tonic contractions. These findings indicate that, in the rat intestine, significant regional differences exists in Ca++ pools mobilized by different activating stimuli and in sensitivity to the blocking action of drugs which interfere with Ca++ mobilization from either intra- or extracellular Ca++ pools.

Animals↗
PubMed1985

Inhibitory effect of GABA on sympathetic neurotransmission in rabbit ear artery.

GABA 100 microM inhibited neurogenic vasoconstrictor responses elicited in rabbit ear artery by field stimulation at various frequencies. GABA was ineffective both on resting tone and on noradrenaline (0.05-5 microM)- and high-K+ (24-54 mM)-induced tonic contraction. GABA effectiveness against field stimulation-induced vasoconstriction was inversely related to the frequency of stimulation. This action of GABA was mimicked by a selective GABAB agonist, such as baclofen (100 microM), but not by selective GABAA agonists as muscimol (100 microM) and homotaurine (100 microM). The selective GABAB antagonists 5-aminovaleric acid (1 mM) and homotaurine (100 microM) completely suppressed the inhibitory effect of GABA on field stimulation-induced vasoconstrictions. GABA action was partially reversed also by the selective GABAA antagonist picrotoxin (100 microM); however, this drug "per se" determined an increase in amplitude of field stimulation-induced contractions which in turn could have determined the minor effect of GABA. As a whole these data suggest that GABA can inhibit sympathetic neurotransmission in rabbit ear artery through the stimulation of a prejunctional receptor of the GABAB subtype.

Amino Acids↗
PubMed1985

Dual effects of clonidine on micturition reflex in urethane anesthetized rats.

The effects of clonidine (CLO) on reflexly activated bladder motility have been examined in urethane-anesthetized rats and compared to its effects on field stimulation-induced contractions of isolated urinary bladder. Intravenous CLO suppressed micturition reflex transiently in a yohimbine-sensitive manner. The suppressive effect of i.v. CLO was greater after surgical sympathectomy (bilateral section of the hypogastric nerves). Intracisternal CLO was more effective than topical (on the bladder dome) or intracerebroventricular CLO in suppressing micturition. When tested in experimental conditions involving activation of both excitatory and inhibitory reflexes to the bladder CLO produced either inhibitory and/or excitatory effects on bladder motility in dependence of factors such as dose, route of administration and integrity of the sympathetic (inhibitory) innervation to the bladder. CLO suppressed bladder contractions produced by dimethylphenilpiperazinium, a ganglionic stimulant, and reduced those produced by postganglionic nerve stimulation. CLO inhibited, in a yohimbine-sensitive manner, amplitude of field stimulation-induced contractions of isolated rat bladder, and its effectiveness was inversely related to the frequency of stimulation. Our findings are suggestive that the inhibitory action of CLO on micturition reflex is counteracted, in normal animals, by a negative feedback on sympathetic inhibitory influences carried out through the hypogastric nerves.

Anesthesia↗
PubMed1985

Influence of "selective" antimuscarinic agents on gastric acid secretion and motility.

The effects of antimuscarinic agents, claimed as acting selectively on gastric acid secretion (pirenzepine) or gut motility (secoverine) or lacking selectivity (atropine and ipratropium bromide), were assayed on both functions by means of two simple experimental models: the gastric acid secretion induced by pylorus ligation and the gastric emptying of a high viscosity meal in the conscious rat. When the same experimental conditions were used in the two tests (i.v. route; duration of the test: 1 hr) we found that pirenzepine was not more selective than atropine on either function while ipratropium bromide was 16 times more selective for gastric secretion and secoverine 2.6 times more selective for gastric motility. Even if routes of administration and times of duration were different between the two tests, similar results were obtained. It was concluded that, when compared to atropine, in our in vivo experimental conditions pirenzepine and secoverine show a scant if any selectivity for either function, while, paradoxically, a sharp selectivity for gastric secretion is shown by the bronchodilator ipratropium bromide.

Animals↗
PubMed1984

The effects of topical capsaicin on rat urinary bladder motility in vivo.

The effects of topical capsaicin on urinary bladder motility were investigated following saline-induced distension of the bladder wall in urethane-anaesthetized rats and compared to the effects of topical substance P and acetylcholine. Capsaicin and substance P produced similar excitatory effects in both quiescent and rhythmically contracting bladders, i.e., a TTX resistant tonic contraction followed by a series of rhythmic, TTX sensitive, phasic contractions. Acetylcholine, in doses equieffective in producing TTX resistant contractions was less effective than capsaicin or substance P in triggering neurogenic rhythmic contractions of bladder muscle. Atropine pretreatment prevented the neurogenic component of the excitatory effect of both capsaicin and substance P. Repeated applications of capsaicin but not of substance P led to desensitization. Bladders of animals pretreated (4 days before) with a large dose of s.c. capsaicin developed insensitivity to topical capsaicin and a larger volume of saline was required to trigger neurogenic rhythmic contractions of the detrusor muscle. These results suggest that capsaicin acts by interfering with the mechanism(s) regulating the threshold for the micturition reflex to occur.

Acetylcholine↗
PubMed1984

The effect of nifedipine and verapamil on KC1-induced rhythmic contractions of guinea pig ureter in vitro.

Addition of KC1 (40 mM) produced rhythmic contractions of guinea-pig ureters in vitro which were unaffected by phentolamine, atropine or tetrodotoxin. KC1 failed to elicit rhythmic contractions of ureters incubated in a Krebs solution with no added Ca++; in these conditions the addition of CaC12 in concentrations of 1.5 mM, or higher, produced rhythmic contractions whose frequency, but not amplitude, was proportional to CaC12 concentration in the bathing medium. EDTA reduced the frequency of KC1-induced rhythmic contractions without affecting their amplitude. Nifedipine and verapamil reduced both the frequency and the amplitude of KC1-induced rhythmic contraction; verapamil was more effective than nifedipine in reducing their amplitude. Urethane reduced the amplitude without significantly affecting the frequency of KC1-induced rhythmic contractions. An increase in the extracellular Ca++ concentration reverted the suppressive effect of all drugs under study. These results suggest that an influx of Ca++ from the extracellular space is responsible for the initiation of KC1-induced rhythmic contractions and is involved in the mechanism(s) which regulates their frequency, but that a separate mechanism regulates their amplitude.

Animals↗
PubMed1984

An analysis of the effects of urethane on cardiovascular responsiveness to catecholamines in terms of its interference with Ca++ mobilization from both intra and extracellular pools.

Urethane (1 X 10(-2) - 1 X 10(-1) M) reduced, in a concentration-dependent manner, both intra and extracellular Ca++ dependent noradrenaline-induced contractions of perfused rabbit ear artery as well as the tonic contractions produced by perfusion with high K+ solution. However, a quantitative analysis of the data indicated that for urethane concentrations similar to those found in plasma during anesthesia urethane antagonism is confined to noradrenaline-induced contractions which depend upon the mobilization of Ca++ from intracellular storage sites. In KCl-contracted arteries, urethane enhanced the relaxant effects of isoprenaline. - Urethane reduced the amplitude of contractions of spontaneously beating guinea-pig right atrium at concentrations which have only a limited effect on frequency. In addition, it decreased in a concentration-dependent manner the amplitude of isoprenaline-activated electrically driven, and K+ depolarized guinea-pig right ventricular strips. Urethane had no effect on the chrono and inotropic actions of isoprenaline on cardiac preparations. In in vivo experiments the chronotropic response to low doses of isoprenaline was significantly higher in urethane-treated as compared to unanesthetized rats. The higher dose of isoprenaline tested produced a significant fall in systolic blood pressure in urethane-anesthetized rats. A significant correlation exists between the chronotropic response to isoprenaline and resting heart rate values in urethane-anesthetized rats. These results indicate that urethane, at concentrations similar to those found in plasma during anesthesia selectively interferes with mobilization of Ca++ from intracellular storage sites. In addition, the interference of urethane anesthesia with the isoprenaline chronotropic effect 'in vivo' cannot be explained by a direct interference of urethane with beta-adrenoceptors at cardiac level.

Animals↗
PubMed1984

Eserine-induced hypertone of guinea pig distal colon in vivo: a new pharmacological procedure for testing smooth muscle relaxants.

A new in vivo procedure suitable for testing the smooth muscle relaxant properties of a test substance is described. Topical eserine produced a long-lasting steady increase in tone of guinea pig distal colon and enhanced the atropine-sensitive phasic activity. Intravenously administered atropine, pirenzepine, and dicyclomine (which possess competitive antimuscarinic properties) produced a dose-related inhibition of eserine-induced muscle tone and suppressed phasic contractions. On the other hand, verapamil and octylonium bromide (which produce smooth muscle relaxation by interfering with Ca++ availability for contraction) did not suppress phasic contraction although they were fully effective in inhibiting eserine-induced tone. The eserine-induced contraction of guinea pig distal colon appears to be a suitable, quick, and inexpensive test for evaluating the effects of potential smooth muscle relaxants against background hypermotility produced by amplifying the neurogenic drive to the target organ.

Animals↗
PubMed1984

The effect of urethane and thiopental sodium on platelet aggregation in vitro and in vivo.

The potential in vitro (heparinized or citrated PRP) and in vivo effects of urethane and thiopental sodium on arachidonic acid, collagen, or ADP-induced rat platelet aggregation has been investigated. Both anesthetics antagonized platelet aggregation in vitro at concentrations higher than those found in plasma during anesthesia. Neither anesthetic altered the piastrinopenia induced by intravenous administration of these aggregating agents. These findings suggest that both anesthetics are suitable for in vivo platelet aggregation studies.

Adenosine Diphosphate↗