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S Manzini

Publications and source records attributed to S Manzini.

At least 127 records · Page 7Linked to original sources
PubMed1988

Differential temperature-dependency of electrophysiological and inotropic actions of nifedipine, verapamil and cinnarizine in K+-depolarized ventricular myocardium.

1. Temperature dependency (in the range 27-37 degrees C) of inotropic and electrophysiological effects of equieffective (EC30 at 37 degrees C) concentrations of nifedipine, verapamil and cinnarizine was assessed in potassium depolarized isoprenaline-reactivated guinea-pig ventricular strips. 2. Lowering temperature greatly enhanced nifedipine inhibition of (a) maximal rate of depolarization (Vmax) of slow action potentials and (b) amplitude of contractions. 3. Electrophysiological and inotropic actions of verapamil was virtually unaffected by temperature changes. 4. Negative inotropic action of cinnarizine was greater at 37 degrees C than at lower temperature. At 37 degrees C, but not at 32 degrees C, cinnarizine reduced Vmax of slow action potentials.

Action Potentials↗
PubMed1988

Regulation of voltage-dependent excitatory responses to alpha,beta-methylene ATP, ATP and non-adrenergic nerve stimulation by dihydropyridines in the guinea-pig vas deferens.

Simultaneous recordings of mechanical and intracellular electrical activity were obtained from the guinea-pig vas deferens, where nerve stimulation, ATP and the stable nucleotide analogue alpha,beta-methylene ATP elicited excitatory responses. Excitatory junction potentials and action potentials were elicited by low-frequency (trains of pulses, generally less than or equal to 2 Hz) field stimulation. alpha,beta-Methylene ATP and ATP elicited only concentration-dependent depolarizations at low concentrations, while higher concentrations elicited a superimposed action potential discharge which was accompanied by mechanical contraction. The voltage threshold at which action potential discharge was initiated by these three stimuli was about -45 mV (resting membrane potential averaged -66 mV). Action potential discharges and contractile responses were antagonized by nifedipine and augmented by Bay K 8644 at concentrations (1 and 0.5 microM, respectively) which exhibited only small effects on either excitatory junction potential amplitudes or nucleotide-induced depolarizations. Bay K 8644 enhanced and nifedipine antagonized the repolarization (rectification) phase of action potential discharge elicited by nerve stimulation and drugs; after-hyperpolarizations were prominent in the presence of Bay K 8644 (0.1-5 microM). Excitatory junction potentials were antagonized after exposure to alpha,beta-methylene ATP. This antagonistic effect of alpha,beta-methylene ATP was also observed following depolarizations elicited in the absence and presence of nifedipine (1 microM). Noradrenaline was approximately 50-100 times less potent than alpha,beta-methylene ATP in eliciting action potential discharge and contraction. It was only when a high concentration of noradrenaline was used (about 60-100 microM) that the noradrenaline-induced depolarization attained the voltage threshold for action potential initiation. These results illustrate the similarity of the electrical components which underlie excitation by nerve stimulation and adenine nucleotides in the vas deferens, and demonstrate the ability of dihydropyridines to regulate voltage-dependent events associated with both the generation and inactivation of muscle action potentials. These are probably voltage-dependent calcium currents and calcium-activated potassium currents, respectively. Neither excitatory junction potentials nor the mechanism of desensitization of the ATP purinoceptor by alpha,beta-methylene ATP involve voltage-dependent calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Simultaneous release by bradykinin of substance P- and calcitonin gene-related peptide immunoreactivities from capsaicin-sensitive structures in guinea-pig heart.

Both bradykinin and capsaicin infusion evoked a marked increase in the outflow of substance P- (SP-LI) and calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) from guinea-pig isolated, perfused heart. After acute exposure to capsaicin in vitro, or in hearts taken from animals pretreated in vivo with capsaicin, bradykinin failed to induce any release. The positive chronotropic effect of bradykinin was reduced after acute capsaicin administration. The effect of bradykinin in the guinea-pig heart could be mediated, at least partly, by release of neuropeptides from peripheral endings of capsaicin-sensitive sensory neurones.

Animals↗
PubMed1988

Resolution and pharmacological properties of the enantiomers of the potent alpha-adrenoceptor antagonist 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl)piperazine.

Resolution of the optical isomers of the alpha-adrenoceptor antagonist IP-66 (1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl)piperazine) and its intermediate IP-30 (1-[2-hydroxy-2-(3'-pyridyl)ethyl]-4- (2'-methoxy-phenyl)piperazine have been carried out. Optical purity was assayed by high-pressure liquid chromatography. The antagonistic potencies of racemic mixtures and stereoisomers toward phenylephrine- and norepinephrine-induced contraction in isolated rat aortic strips have been compared. (+)-IP-66 and (+)-IP-30 were resp. 363 and 170 times more potent than respective (-) isomers in eliciting competitive alpha 1-adrenoceptor blockade. Similarly IP-66 (+) or (+/-) were extremely more effective than the (-) isomer in antagonizing norepinephrine-induced pressor responses in pithed rat.

Adrenergic alpha-Antagonists↗
PubMed1988

Further studies on the pharmacodynamic properties and organ selectivity of octylonium bromide.

At concentrations ranging from 8.5 to 30 microM, octylonium bromide (OB) did not affect sodium channel availability measured as maximal rate of depolarization (Vmax) of cardiac action potential. On the other hand, at equieffective spasmolytic concentrations (1.1 mM), procaine markedly inhibited Vmax as well as other electrophysiological parameters. These experiments indicate that at fully effective spasmolytic concentrations OB is devoid of local anaesthetic properties. In concentrations up to 10 microM OB did not affect phosphodiesterase activity in crude homogenates of rat colon which were inhibited by both papaverine (EC50 = 0.7 mM) and theophylline (EC50 = 3.5 mM). OB was more effective in antagonizing spasmogen-induced contractions on colonic as compared to tracheal preparations. Inhibition of Neurohormone-induced calcium ion mobilization from cellular and extracellular pools remains the mechanism of action which best explains the spasmolytic effects of OB on intestinal smooth muscle.

Action Potentials↗
PubMed1987

Blockade by theophylline of capsaicin-induced motor effects in guinea-pig airways.

The effect of theophylline was tested on the capsaicin-induced increase in insufflation pressure in anaesthetized guinea-pigs and contraction of isolated tracheal spirals. Theophylline (6.25-25 mg/kg i.v.) inhibited in a marked, prolonged and dose-related manner the increase in insufflation pressure elicited by i.v. injection of capsaicin (2-10 micrograms/kg). Theophylline, even at plasma concentrations as low as 15-23 micrograms/ml (which are within or slightly higher than the therapeutic range in humans) produced an inhibition of about 30-50% of capsaicin-induced bronchospasm. Theophylline was significantly less effective in antagonizing the bronchospasm elicited by maximally effective dose (100 micrograms/kg i.v.) of acetylcholine as well as by a dose equieffective to capsaicin 10 micrograms/kg (i.e. acetylcholine 50 micrograms/kg). Theophylline (30 microM-1 mM) also inhibited potently and concentration dependently the capsaicin-induced contraction in vitro and, again, it was significantly less effective against cholinomimetic-induced responses. These data suggest that theophylline can interfere, at therapeutic doses, with some process(es) selectively involved in capsaicin-induced neuropeptide-mediated bronchoconstriction. Since capsaicin-sensitive sensory fibers are thought to be involved in the pathogenesis of bronchial hyperreactivity and asthma, these inhibitory actions of theophylline might be relevant for its therapeutic effects.

Acetylcholine↗
PubMed1987

Cutaneous lesions in capsaicin-pretreated rats. A trophic role of capsaicin-sensitive afferents?

1. The time course and regional distribution of 'spontaneous' cutaneous lesions in rats desensitized to capsaicin as newborns was correlated to behavioural observations and regional distribution of substance P-like immunoreactivity (SP-LI) and tachykinin-like immunoreactivity (TK-LI) in various skin areas. 2. 'Spontaneous' skin lesions in the form of wounds, scabs and areas of alopecia were observed in 80-90% of rats desensitized to capsaicin. No major sex-related differences were observed with regard to incidence and distribution of the lesions with the possible exception of a lesser tendency to bilateral lesions in female rats. 3. 'Spontaneous' skin lesions were almost restricted to the head: the areas most frequently affected were snouts, periocular and retroauricular regions and ventral area of the neck. 4. No major differences were observed between capsaicin- or vehicle-treated animals in spontaneous or novelty-induced grooming as well as in open-field gross behaviour. Likewise, no differences were observed in the mouse-killing behaviour. 5. Both SP-LI and TK-LI in various skin areas were significantly reduced by systemic capsaicin pretreatment. The rank order of various skin areas for SP-LI or TK-LI levels was: snouts greater than thigh greater than neck greater than abdomen approximately equal to retroauricular region. 6. Intradermal injection of Arg-neurokinin B, a potent and water soluble derivative of neurokinin B, produced a similar plasma extravasation (Evans blue leakage technique) in the skin of vehicle- or capsaicin-pretreated rats. 7. In capsaicin-desensitized rats fur regrowth (measured at abdominal level, 28 days after shaving) was significantly less than in vehicle-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Contribution of neurogenic and myogenic factors in the response of rat proximal colon to distension.

The response of the rat proximal colon to distension and drugs that interfere with intrinsic and extrinsic nerves was investigated in vivo (urethan anesthesia) and in vitro. Saline distension induced the appearance of a cyclic contractile activity that was slightly inhibited by atropine (ATRO) and enhanced by physostigmine. Hexamethonium increased the distension-induced motor activity. Topical tetrodotoxin (TTX), lidocaine, or procaine produced an increase in motility of the proximal colon. Isolated segments of the proximal colon exhibit a high-amplitude phasic contractile activity that was increased by stretching, transiently inhibited by ATRO, unaffected by hexamethonium, and increased by TTX. The effects of both ATRO and TTX were more evident at high- than low-resting tone. In the presence of ATRO plus guanethidine, field stimulation of the isolated rat proximal colon suppressed the spontaneous contractile activity of the preparations. These findings indicate that, in the proximal colon of urethan-anesthetized rats, a tonic discharge of intramural nonadrenergic noncholinergic neurons suppresses the inherent myogenic contractile activity of the smooth muscle cells. Extrinsic nervous supply plays a subsidiary role in maintaining colonic motility.

Animals↗
PubMed1986

An electrophysiological analysis of the effect of reactive blue 2, a putative P2-purinoceptor antagonist, on inhibitory junction potentials of rat caecum.

The electrophysiological effects of the putative P2-purinoceptor antagonist reactive blue 2 (RB2) were investigated in strips of circular muscle of rat caecum with the sucrose gap technique. RB2 (0.1-1 mM) antagonized in a concentration-dependent manner, the amplitude, rate of rise and speed of onset of the inhibitory junction potentials elicited either with single pulse or with train of field stimulation at 10 Hz. A fully effective concentration of RB2 (0.5 mM) decreased the membrane response to high strength hyperpolarizing constant current pulses, thus indicating an increase in membrane conductance. At this concentration RB2 inhibited the hyperpolarization induced by the stable ATP analogue alpha,beta-methylene ATP, but did not significantly inhibit noradrenaline-induced hyperpolarization. RB2 (0.5 mM) also abolished the ability of carbachol to elicit spikes, while the carbachol-induced depolarization and the amplitude of accompanying mechanical responses were largely unaffected. The possible mechanisms responsible for the RB2-induced effects are discussed.

Animals↗
PubMed1986

Pharmacological evidence that at least two different non-adrenergic non-cholinergic inhibitory systems are present in the rat small intestine.

The nature of the non-adrenergic non-cholinergic (NANC) relaxation was studied in the proximal (duodenum) and distal (ileum) regions of the rat small intestine. In rat duodenum ATP (1 microM-1 mM) produced a concentration-dependent transient relaxation. In ileal segments it produced a slight inhibitory effect at low concentrations (1-10 microM) and a powerful concentration-dependent contractile effect at concentrations equal to or higher than 100 microM. Relaxation similar to that elicited by ATP can be induced in rat duodenum with the nicotinic stimulant dimethylphenylpiperazinium (DMPP, 0.1 mM) and with gamma-aminobutyric acid (GABA, 1 mM). DMPP had a similar inhibitory effect on distal ileum while GABA barely affected spontaneous activity in this preparation. TTX (0.5 microM)-sensitive relaxation can be elicited in both duodenal and ileal tissues by field stimulation at 0.1 Hz. In the rat duodenum this nerve-mediated relaxation was sensitive to ATP desensitization, nucleotide pyrophosphatase (0.25 U/ml) but resistant to the proteolytic enzyme alpha-chymotrypsin (2 U/ml). On the other hand the field stimulation (0.1 Hz)-induced relaxation in the distal ileum was unaffected by ATP desensitization (by using both low or high concentration of ATP) and by incubation of the preparation with the two enzymes. These findings provide pharmacological evidence that low frequency field stimulation activates at least two different inhibitory NANC systems in the rat small intestine. Adenosine-5'-triphosphate (ATP) appears to be involved as a major transmitter in the duodenal but not in the ileal NANC inhibitory mechanism(s).

Adenosine Triphosphate↗
PubMed1986

Capsaicin activates neurogenic non-adrenergic non-cholinergic relaxations of the isolated rat duodenum.

Capsaicin induces a transient relaxation of the isolated rat duodenum in the presence of atropine plus guanethidine. The relaxant effect of capsaicin was not observed in vitro in the duodenum of capsaicin-pretreated animals. Capsaicin-induced relaxation was antagonized by tetrodotoxin or cold storage (24 h at 4 degrees C). It is concluded that capsaicin produces a neurogenic relaxation of the rat duodenum by activating an intramural non-adrenergic non-cholinergic mechanism which inhibits intestinal motility.

Animals↗
PubMed1986

Extrinsic origin of the capsaicin-sensitive innervation of rat duodenum: possible involvement of calcitonin gene-related peptide (CGRP) in the capsaicin-induced activation of intramural non-adrenergic non-cholinergic neurons.

Capsaicin produces a concentration-related relaxation of the longitudinal muscle of the rat isolated duodenum in the presence of atropine (3 microM) plus guanethidine (3 microM). This effect of capsaicin is partly (about 40%) antagonized by tetrodotoxin (1.0 microM) suggesting the involvement of intramural non-adrenergic non-cholinergic (NANC) neurons. The capsaicin-induced relaxations are unaffected by previous bilateral vagotomy or removal of the inferior mesenteric ganglion but are completely prevented by removal of the coeliac ganglia plus the superior mesenteric ganglion (72 h before). Acute duodenal denervation did not modify the response to capsaicin. Unlike various neuropeptides (substance P, kassinin, neurokinin A, cholecystokinin octapeptide, somatostatin, vasoactive intestinal polypeptide) only the calcitonin gene-related peptide (CGRP) closely mimicked, both qualitatively and quantitatively, the capsaicin-induced relaxations. The CGRP-induced relaxations were unaffected by hexamethonium and partly reduced (about 40%) by tetrodotoxin. In preparations desensitized to adenosine-triphosphate (ATP) a putative NANC inhibitory neurotransmitter of the rat duodenum, the effects of CGRP were reduced (about 30%) as compared to controls. After ATP-desensitization tetrodotoxin did not produce any further reduction of the CGRP-induced relaxations suggesting the involvement of endogenous ATP in the neuronal (tetrodotoxin-sensitive) component of the CGRP-induced relaxations. Either ATP- or CGRP-desensitization reduced (about 50 and 65% respectively) the amplitude of the capsaicin-induced relaxations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1986

Effect of temperature on isoprenaline- and barium-induced slow action potentials in guinea-pig ventricular strips.

The effect of variation in temperature (37-32 and 27 degrees C) on electrical and mechanical activity of depolarized and isoprenaline- or barium-reactivated guinea pig ventricular strips was studied. Lowering the temperature brings a marked prolongation of isoprenaline-induced slow action potentials. In addition the maximal rate of depolarization was strongly reduced at lower temperatures. These effects were observed at an extracellular Ca2+ concentration of either 0.9 or 2.5 mM. The accompanying mechanical activities was significantly increased by reduction in temperature. Barium-induced slow action potentials were similarly affected by temperature variations. These observations suggest that hypothermia exert a sort of calcium antagonistic action probably coupled to a reduction of repolarizing outward potassium currents.

Action Potentials↗
PubMed1986

Positive inotropic effect of Mg2+ in K+-depolarized isoprenaline-reactivated guinea-pig ventricular strip.

In K+-depolarized isoprenaline-reactivated guinea-pig ventricular strips increase in external Mg2+ concentration produced a biphasic inotropic effect i.e. at low concentrations (2.5-7.5 mM) a slight negative inotropic effect was observed, while at higher Mg2+ concentrations (10-17.5 mM) a strong positive inotropic effect become predominant. Variation in extracellular K+ concentration (17-22 and 25 mM) determined a concentration related reduction in Mg2+-induced positive inotropic effect. Increase in extracellular Ca2+ concentration (2.5-3.6 and 5.4 mM) prevented the development of Mg2+-induced negative inotropic effect but did not affect the magnitude of the positive inotropic effect. Mg2+-induced positive inotropic effect was unaffected by TTX (3 mg/l) and even enhanced by nifedipine (65 nM). Caffeine (0.2-15 mM) antagonized in a concentration dependent manner the positive inotropic effect of Mg2+. On the other hand in the presence of Mg2+ (15 mM) caffeine (0.2 mM) was unable to exert its positive inotropic effect. Mg2+ (15 mM) determined a "Ca2+ entry blocking"--like modifications of electrophysiological parameters of slow action potentials elicited by isoprenaline in K+-depolarized preparations. Such effects of Mg2+ were also present during the positive inotropic effect. The possible mechanisms responsible for these complex inotropic effects of Mg2+ are discussed.

Action Potentials↗
PubMed1986

GABA A receptor mediated neurogenic inhibition of motility in the small intestine of urethane-anaesthetized rats.

Intravenous GABA (0.1-3 mg/kg) induced transient relaxation of the duodenum in urethane anaesthetized rats. The effect of GABA was mimicked by homotaurine and antagonized by bicuculline, suggesting the involvement of GABA A receptors in this type of response. Duodenal relaxation induced by GABA was unaffected by i.v. hexamethonium, phentolamine propranolol or 6-hydroxydopamine but was prevented in preparations pretreated with topical tetrodotoxin thus indicating its neurogenic origin. The ability of GABA to induce neurogenic relaxation decreased rapidly when increasing the distance from the duodenum while relaxations induced by DMPP or noradrenaline were observed throughout the whole rat small intestine.

Anesthesia↗