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Biomedical subjects

C A Maggi

Publications and source records attributed to C A Maggi.

At least 559 records · Page 31Linked to original sources
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

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↗
PubMed1985

Cytoprotective approach to peptic ulcer therapy: a preliminary dose-finding clinical investigation with triletide.

Thirty out-patients with gastric (8) or duodenal (22) ulcers were randomly assigned to receive a daily dose of 1.0, 1.5 or 2.0 g triletide over a period of 8 weeks. Endoscopic findings and overall clinical rating indicated that triletide effectively accelerated ulcer healing in a proportion of patients (73% of responders), with a trend for better response at doses higher than 1 g/day, regardless of the ulcer location. Heartburn, epigastric pain and concomitant antacid consumption improved significantly in each dose group, but to a significantly greater extent in the highest dose group than in either mid-dose or low-dose groups. Tolerance of treatment was good at all dose levels, and no significant variations in routine haematology, haematochemistry or renal function tests were observed. It is suggested, therefore, that triletide provides an effective and well-tolerated new means to promote ulcer healing, both gastric and duodenal, with easily graded symptomatic relief by modifying the daily dose.

Adult↗
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↗
PubMed1984

Evidence that GABAA receptors mediate relaxation of rat duodenum by activating intramural nonadrenergic-noncholinergic neurones.

GABA produced rapid and transient relaxation of rat duodenum. Homotaurine (3-aminopropansulphonic acid) but not (+/-)-baclofen had a GABA-like effect. GABA-induced relaxation was almost completely inhibited by tetrodotoxin but was unaffected by atropine. Cross desensitization developed between GABA and homotaurine but not between GABA and (+/-)-baclofen. The concentration response curve to the relaxant effects of GABA was shifted to the right by both bicuculline and picrotoxin. However maximal relaxation was still produced by GABA in the presence of bicuculline but not in the presence of picrotoxin. GABA-induced relaxation was not affected by prazosin, yohimbine, propranolol or reserpine pretreatment. Field stimulation (0.1 Hz) of rat isolated duodenum in the presence of atropine and guanethidine produced relaxation similar to that produced by GABA. The ganglionic stimulant DMPP produced a similar effect. Neither Met-enkephalin, noradrenaline, 5-HT, histamine, VIP or arachidonic acid could be held responsible for GABA-induced neurogenic relaxation of rat duodenum. ATP produced relaxations which closely mimicked those produced by either GABA or field stimulation. Exposure to ATP desensitized responses to both GABA and field stimulation to about the same extent. ATP, GABA and field stimulation-induced relaxation was unaffected by either theophylline or indomethacin, but was significantly and selectively antagonized by apamin. In conclusion, GABA-induced relaxation of rat isolated duodenum is largely dependent upon activation of intra-mural nonadrenergic-noncholinergic neurones. The GABA receptor involved appears to be of the GABAA subtype. Circumstantial evidence is provided indicating that ATP might be the endogenous substance released by GABA.

Animals↗
PubMed1984

GABAB receptor mediated inhibition of field stimulation induced contractions of detrusor muscle strips from newborn rats.

The effect of GABA on field stimulation (0.1 Hz) induced contractions have been examined on detrusor strips from adult and newborn rats. Field stimulation induced contractions were unaffected by hexamethonium (10(-5) M) but almost suppressed by tetrodotoxin (5 X 10(-7) M) in both age groups. Atropine (3 X 10(-6) M) produced a marked inhibition of twitches in detrusor strips from newborn rats but only a slight (10% or less) inhibition in strips from adult animals. Neither GABA (10(-4), homotaurine (10(-3) M) or (+/-)-baclofen (10(-4] affected twitches in detrusor strips from adults rats. On the other hand both GABA and (+/-)-baclofen inhibited, to about the same extent (55-60% inhibition) twitches in detrusor strips from newborn animals. Homotaurine had no significant effect. The effects of both GABA (10(-4) M) and (+/-)-baclofen (10(-4) M) on twitches in detrusor strips from newborn rats were reduced if the preparations were previously exposed to a low concentration of GABA (5 X 10(-6) M) thus indicating desensitization. The inhibitory effect of GABA on twitches in newborn rats were concentration dependent in the range of 10(-7) to 10(-4) M. The GABAA receptor antagonist picrotoxin (10(-4) M) had no effect on the GABA concentration response curve whereas the GABAB receptor antagonist, homotaurine, produced an antagonism of the competitive type. The calculated pA2 value for the GABA-homotaurine interaction was 4.4 +/- 0.07. Neither GABA (10(-4) M) nor (+/-)-baclofen (10(-4) M) produced any significant inhibition of acetylcholine (2 X 10(-7) M) induced contractions of detrusor of strips from newborn rats, while atropine (3 X 10(-6) M) completely suppressed them. These results indicate that GABA inhibits field stimulation induced contractions of detrusor strips from newborn rats by activating prejunctional receptors (presumably of the GABAB subtype) which inhibit the release of acetylcholine from the postganglionic nerve endings.

Aging↗
PubMed1984

Differential effects of vasodilators on the mobilization of calcium pools during contractions of rabbit ear artery induced by noradrenaline and high potassium.

The effects of some vasodilators on the mobilization of different Ca2+ pools during contractions produced by noradrenaline and high K+ medium in rabbit ear artery has been investigated. Sodium nitrite was much more effective in antagonizing high K+-stimulated Ca2+ fluxes through the potential-dependent Ca2+ channels than noradrenaline-induced mobilization of intracellular Ca2+ stores or Ca2+ fluxes through receptor-operated channels. Papaverine was only slightly more active on contractions sustained by influx of extracellular Ca2+ (through potential-dependent channels and receptor-operated channels) than on those sustained by intracellular Ca2+. Verapamil and nifedipine were much more effective in antagonizing contractions sustained by Ca2+ entry through potential-dependent channels than through receptor-operated channels. Nifedipine was completely ineffective in antagonizing noradrenaline-induced mobilization of intracellular Ca2+ stores while verapamil had a limited inhibitory action in high concentrations. Phentolamine was equieffective in antagonizing both types of noradrenaline-induced contractions while having no effect on high K+-induced tonic contraction.

Animals↗
PubMed1984

GABAB receptor mediated inhibition of field stimulation-induced contractions of rabbit bladder muscle in-vitro.

The effects of GABA and selective GABAA and GABAB receptor agonists and antagonists have been investigated on field stimulation-induced contractions (0.1 Hz) of rabbit urinary bladder strips in-vitro. Atropine inhibits twitches of bladder strips obtained from the bladder dome more effectively than those obtained from the bladder base. Both GABA and the selective GABAB receptor agonist, (+/-)-baclofen inhibited field stimulation-induced contractions to about the same extent, while the selective GABAA receptor agonist, homotaurine had no effect. In the presence of atropine, GABA failed to inhibit further the amplitude of twitches. The effects of either GABA or (+/-)-baclofen were antagonized by the GABAB receptor antagonists homotaurine and 5-aminovaleric acid, while the GABAA receptor antagonist picrotoxin had no effect. Neither GABA nor (+/-)-baclofen had any significant effect on acetylcholine-induced contractions of unstimulated bladder strips, but they were abolished by atropine. These results suggest that GABAB receptors inhibit field stimulation-induced contractions of rabbit bladder muscle by reducing the amount of acetylcholine released per nerve impulse.

Acetylcholine↗