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Biomedical subjects

A Meli

Publications and source records attributed to A Meli.

At least 109 records · Page 6Linked to original sources
PubMed1988

Contractile response of the human isolated urinary bladder to neurokinins: involvement of NK-2 receptors.

The contractile response to substance P (SP), neurokinin A (NKA) and arginin-neurokinin B (Arg-NKB) (a water soluble analogue of NKB) was investigated in detrusor muscle strips from the dome of the urinary bladder obtained from patients undergoing total cystectomy for carcinoma of the bladder base. Spontaneous activity and response to nerve stimulation indicated that the material used in this study has characteristics similar to those described for 'normal' human detrusor muscle. All neurokinins induced a concentration-related contraction with sensitivity at nM concentrations and the following rank order of potency: NKA (90) greater than Arg-NKB (22) greater than SP (1). These findings indicate the involvement of NK-2 receptors in the contractile response of human detrusor muscle to neurokinins.

Aged↗
PubMed1988

Prostanoids modulate reflex micturition by acting through capsaicin-sensitive afferents.

Topical application of exogenous prostanoids (PGE2, TBX B2) on the serosal surface of the urinary bladder of urethane-anaesthetized rats activated reflex micturition. Likewise, intravesical instillation of PGE2 during the cystometrogram lowered the threshold for reflex micturition. Both effects were prevented by systemic capsaicin desensitization (50 mg/kg s.c., 4 days before). Indomethacin pretreatment and systemic capsaicin desensitization each increased the micturition threshold without affecting the amplitude of micturition contraction. However, the effect of the two treatments combined was not greater than the effect of either alone. These findings support the idea that endogenous prostanoids facilitate reflex micturition by stimulating or sensitizing, directly or indirectly, the subset of bladder mechanoreceptors which is capsaicin-sensitive in adult rats.

Animals↗
PubMed1988

Capsaicin-sensitive afferents in the rat urinary bladder activate a spinal sympathetic cardiovascular reflex.

In urethane-anesthetized rats with an intact spinal cord, application of capsaicin on the outer surface of the urinary bladder produced a transient bradycardia, hypotension and negative cardiac inotropism which were neither prevented by i.v. atropine (0.5 mg/kg) nor by cervical vagotomy. In acute spinal rats (C2-C3) application of capsaicin (0.2 and 2 micrograms in 25 microliters) on the urinary bladder induced a transient hypertension, tachycardia and positive cardiac inotropism. A second application (30 min later) induced minor cardiovascular effects, expecially with the higher dose, indicating desensitization. All cardiovascular responses to topical capsaicin were abolished by systemic capsaicin desensitization (50 mg/kg s.c., 4 days before). The excitatory cardiovascular response to capsaicin in acute spinal rats was markedly reduced by bilateral section of pelvic but not hypogastric nerves. Further, it was abolished by pretreatment with hexamethonium (20 mg/kg i.v.) or reserpine (5 mg/kg i.p., 2 days before) and reduced, at various extent for the different components, by phentolamine (0.5 mg/kg i.v.) or propranolol (1 mg/kg). In rats with pelvic and hypogastric nerves intact, section of the cord at a level (T12-L1), just above the medullary segments which receive primary afferent input from the bladder (L6-S1), abolished the excitatory cardiovascular response to application of capsaicin on the bladder. In spinal rats (C2-C3) rapid distension of the urinary bladder with saline produced transient tachycardia, hypertension and positive cardiac inotropism similar to that evoked by capsaicin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The effect of omega conotoxin GVIA, a peptide modulator of the N-type voltage sensitive calcium channels, on motor responses produced by activation of efferent and sensory nerves in mammalian smooth muscle.

1. The effect of omega-conotoxin (CTX) GVIA, a peptide which blocks neuronal calcium channels, were investigated on nerve-mediated motor responses in a variety of isolated smooth muscle preparations from rats and guinea-pigs. 2. In the rat or guinea-pig isolated vas deferens CTX (1 nM-1 microM) produced a concentration and time-related inhibition of the response to field stimulation, while the responses to KCl, noradrenaline or adenosine triphosphate were unaffected. In the presence of CTX a series of tetrodotoxin-resistant contractions could be elicited by field stimulation by increasing pulse width and/or voltage. 3. In the rat or guinea-pig isolated urinary bladder, CTX produced a concentration and time-dependent inhibition of twitch responses to field stimulation without affecting the response to exogenous acetylcholine. In the rat bladder the maximal effect did not exceed 25% inhibition while a much larger fraction of the response (about 70%) was inhibited in the guinea-pig bladder. The CTX-resistant response was abolished, in both tissues, by tetrodotoxin. 4. The effects of CTX in the rat bladder were also studied with a whole range of frequencies of field stimulation (0.1-50 Hz). Maximal inhibition was observed toward contractions elicited at frequencies of 2-5 Hz. At low frequencies the inhibitory effects of CTX and atropine were almost additive while at high frequencies of stimulation a large component of the atropine-sensitive response was CTX-resistant. 5. In the rat isolated proximal duodenum, field stimulation in the presence of atropine and guanethidine produced a primary relaxation followed by a rebound contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The contribution of capsaicin-sensitive sensory nerves to xylene-induced visceral pain in conscious, freely moving rats.

1. Intravesical instillation of xylene (10-100%, dissolved in silicone oil) through a catheter implanted into the bladder of conscious, freely-moving rats produced behavioural effects (licking of lower abdomen or perineal region) suggestive of intense visceral pain, not mimicked by topical application of the irritant on the urethral outlet. 2. The xylene-induced visceral pain was prevented, to the same extent, by systemic desensitization to capsaicin (50 mg/kg s.c.) performed in either adult or newborn rats, as well as by extrinsic bladder denervation (pelvic ganglionectomy), thus indicating the involvement of primary afferents in the bladder wall. 3. Other behavioural responses induced by xylene instillation into the bladder (hind limb hyperextension, grooming) were not affected by systemic capsaicin desensitization in either adult or newborn rats, but were abolished by bladder denervation. 4. Systemic capsaicin desensitization produced an almost complete depletion of substance P-, neurokinin A-like and calcitonin gene-related peptide-like immunoreactivity in the rat urinary bladder. 5. These findings indicate that, in addition to their role in activating reflex micturition, the neuropeptides-containing capsaicin-sensitive sensory nerves of the rat bladder are involved in chemogenic visceral pain.

Aging↗
PubMed1988

On the role of endogenous GABA in the forced swimming test in rats.

GABA content was reduced in the nucleus accumbens, cortex and brainstem of rats after 5 but not after 45, 120 min or 24 hr, from the termination of the pretest session. This reduction was not observed in rats performing on rotarod. Intraperitoneal AOAA (25 mg/kg; 24, 5 and 1 hr before the test), reduced at the same extent immobility time regardless whether the animals had been exposed to a pretest session. In pretested animals, reduction in immobility time produced by AOAA (25 mg/kg X 3 times) was similar to that observed following 50 mg/kg, 5 hr before testing. This reduction was not antagonized by GABA antagonists bicuculline (2 mg/kg) or picrotoxin (2 mg/kg), given intraperitoneally 30 and 20 min before the test respectively. Intraperitoneal sodium valproate (200 or 400 mg/kg; 24, 5 and 1 hr before the test) and isoniazide (200 mg/kg) or 4-deoxypyridoxine (400 mg/kg), administered 1 or 1.5 hr before the test, were ineffective. AOAA (25 mg/kg X 3 times) gave a similar increase in GABA levels to 50 mg/kg only once in the brainstem, nucleus accumbens and hypothalamus and a greater increase in the other brain areas. After 5 hr from single dosing, 25 mg/kg AOAA increased GABA levels less than 50 mg/kg AOAA in the brainstem, nucleus accumbens, frontal cortex and striatum, and increased it to same extent in the other areas. Sodium valproate (400 mg/kg X 3 times) increased GABA levels in all brain areas, except hippocampus, although to a lesser extent than AOAA.

Aminooxyacetic Acid↗
PubMed1988

Functional responses to baclofen and 4,5,6,7-tetrahydroisoxazolo (5,4-c) pyridin-3-ol (THIP) in rats repeatedly treated with desipramine.

Subcutaneous chronic desipramine (DMI, 5 mg/kg once daily for 18 consecutive days) prevented subcutaneous THIP (20 mg/kg) reduction in body temperature but did not affect THIP behavioral depressant effect (open-field behavior). Repeated DMI treatment did not affect subcutaneous baclofen (2.5-10 mg/kg) reduction in body temperature and behavioral depression (open-field behavior).

Analgesics↗
PubMed1988

New method for recording cystometrograms in conscious, freely moving rats.

A new cystometric technique has been developed that is suitable for quantitative studies on physiopharmacology of micturition in conscious, freely moving rats. The method involves the transvesical infusion of warm saline at various filling rates through a catheter chronically implanted into the bladder dome. The various parameters of the collecting and voiding phase of the cystometrogram were recorded. Results obtained indicate that characteristics of the bladder voiding cycle of conscious, freely moving rats are qualitatively similar but quantitatively different from those described previously in anesthetized animals.

Animals↗
PubMed1988

The sensory-efferent function of capsaicin-sensitive sensory neurons.

Capsaicin-sensitive sensory neurons convey to the central nervous system signals (chemical and physical) arising from viscera and the skin which activate a variety of visceromotor and neuroendocrine reflexes integrated at various levels (intramurally in peripheral organs, at level of prevertebral ganglia, spinal and supraspinal level). Much evidence is now available that peripheral terminals of certain sensory neurons, widely distributed in skin and viscera have the ability to release, upon adequate stimulation, their transmitter content. In addition to the well-known "axon reflex" arrangement, the capsaicin-sensitive sensory neurons have the ability to release the stored transmitter also from the same terminal which is excited by the environmental stimulus. The efferent function of these sensory neurons is realized through the direct and indirect (i.e. mediated by activation of other cells) effects of released mediators. The action of released transmitters on postjunctional elements covers a wide range of effects which may have a physiological or pathological relevance. Development of drugs capable of controlling the sensory-efferent functions of the capsaicin-sensitive sensory neurons represent a new and very promising area of research for pharmacological treatment of various human diseases.

Animals↗
PubMed1988

The effect of nifedipine on spontaneous, drug-induced and reflexly-activated contractions of the rat urinary bladder: evidence for the participation of an intracellular calcium store to micturition contraction.

1. The effect of nifedipine on spontaneous and stimulated motility of the rat urinary bladder has been investigated in vitro (isolated detrusor strips) and in vivo (micturition reflex). 2. Nifedipine inhibited tone and spontaneous activity of the isolated rat bladder, its effect being greater in indomethacin-treated preparations. Nifedipine suppressed the KCl induced phasic and tonic contraction and inhibited by 60-80% the carbachol- or ATP- induced contractions. Nifedipine reduced by about 70% amplitude of the nerve-mediated bladder contractions. 3. Exposure to Ca free medium containing EDTA suppressed tone and spontaneous activity of the rat bladder. In these conditions the response to KCl or ATP was rapidly abolished while a response to carbachol was still evident even after a long exposure to the Ca free medium. 4. In vivo, nifedipine affected reflex micturition e.g. increased volume threshold and slightly reduced amplitude of micturition contraction. In addition, nifedipine reduced voiding efficiency e.g. increased residual volume after micturition. These effects were evident following ligation of the ureters because in normal conditions nifedipine induced a marked diuresis which masked its effect on volume threshold. 5. These findings indicate that in the rat urinary bladder Ca from both intra- and extracellular pools is mobilized during spontaneous or stimulated contractions. Mobilization of an intracellular Ca pool by cholinomimetics or other neurotransmitter(s) may be responsible for the nifedipine-resistant component of the voiding contraction in vivo.

Adenosine Triphosphate↗
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

Neural pathways and pharmacological modulation of defecation reflex in rats.

1. A new method was developed for quantitative studies on defecation reflex in urethane-anesthetized rats which involves the continuous infusion of saline (0.1 ml/min) to distend a balloon placed in the rectum. At threshold values, the balloon was expelled during an active rectal contraction. 2. Balloon expulsion was greatly delayed or even abolished by i.v. hexamethonium. Cord transection at the upper cervical level increased defecation threshold but a functional, hexamethonium-sensitive response was still elicited in spinal rats. 3. Various parameters of the defecation response were modulated by drugs (phentolamine, picrotoxin, naloxone) expected to interfere (either centrally or peripherally), with neural pathways controlling the autonomic outflow for the reflex response. 4. In capsaicin-pretreated rats (50 mg/kg s.c. on 2nd day of life, experiments performed at 2 months), daily fecal production was unchanged as compared to vehicle-treated, age-matched controls. However, under urethane-anesthesia, defecation threshold was increased at higher-than-normal values by capsaicin-pretreatment. 5. In in vitro experiments, capsaicin (1 microM) induced a transient inhibition of field stimulation-induced contractions of the rat isolated rectum. This effect was mimicked by application of calcitonin gene-related peptide (CGRP) (0.1 microM) while Substance P (0.1 microM) had an opposite effect. In preparations desensitized to exogenous CGRP, the inhibitory effect of capsaicin was almost abolished. 6. These findings indicate that in rats, reflex defecation is mainly organized at spinal level, although the participation of supraspinal centers may modify the functional response. Capsaicin-sensitive afferents may be involved in the initiation of certain forms of reflex defecation, although capsaicin-resistant mechanisms are capable of activating the normal excretory function.

Animals↗
PubMed1988

Propagated motor activity in the small intestine of urethane-anaesthetized rats: inhibitory action of sympathetic and capsaicin-sensitive nerves.

1. In the duodenum/small intestine of urethane-anesthetized rats, a series of atropine- and hexamethonium-sensitive phasic contractions activity were recorded by using a balloon. With two balloons, one in the proximal duodenum (B1) and the other at a distal site (B2) a co-ordinated motor activity was observed which migrated from B1 to B2. 2. Spontaneous activity of the duodenum was greater in either adrenalectomized, guanethidine- or capsaicin-pretreated than in control rats. In guanethidine-pretreated animals a series of atropine-resistant but hexamethonium-resistant rhythmic contractions could be demonstrated. 3. In control rats, distension of the balloon produced an inhibitory effect on rhythmic contractions which were ultimately suppressed. Distension had little inhibitory effect on duodenal motor activity of adrenalectomized, guanethidine- or capsaicin-pretreated rats. 4. These findings indicate that the propagated motor activity in the duodenum/small intestine of urethane anesthetized rats can be modulated by the adrenals as well as sympathetic and capsaicin-sensitive nerves.

Adrenalectomy↗
PubMed1988

Tachykinin-like immunoreactivity in the mammalian urinary bladder: correlation with the functions of the capsaicin-sensitive sensory nerves.

The tachykinin-like immunoreactivity of the urinary bladder has been measured in various species by means of an antiserum (K12) having negligible cross-reactivity with substance P. The rank order for bladder content of tachykinin-like immunoreactivity was guinea-pig greater than mice greater than rat, similar to that found for substance P-like immunoreactivity. In all three species, both substance P- and tachykinin-like immunoreactivities were depleted by systemic capsaicin desensitization. The time course for depletion of substance P- and tachykinin-like immunoreactivities of the rat bladder following extrinsic denervation was almost superimposable. At reverse phase high pressure liquid chromatography, the major constituent of tachykinin-like immunoreactivity of the rat bladder co-eluted with neurokinin A. In vitro, the contractile response of the rat bladder to capsaicin (1 microM) was directly proportional to bladder tachykinin-like immunoreactivity while the response to field stimulation was not. In vivo, the volume threshold for reflex micturition was inversely proportional to bladder tachykinin-like immunoreactivity while amplitude of micturition contraction was not. Similar correlations were found in a previous study for substance P-like immunoreactivity. The contractile response to capsaicin or neurokinin A of the rat isolated bladder were significantly reduced by incubation with phenoxybenzamine at a concentration reported to produce a selective alkylation of neurokinin-2 receptors, while the response to substance P or KCl was unaffected. These findings indicate that multiple neurokinins co-exist in those bladder sensory nerves which are capsaicin-sensitive in adult rats. Both substance P- and tachykinin-like immunoreactivities in the rat bladder appear to be good functional markers of the sensory and "efferent" functions mediated by capsaicin-sensitive nerves, consistent with the hypothesis of a transmitter role for the corresponding peptides.

Animals↗
PubMed1988

The contribution of sensory nerves to xylene-induced cystitis in rats.

The role of capsaicin-sensitive sensory nerves of the rat urinary bladder in xylene-induced cystitis was investigated. Instillation of xylene into the urinary bladder of female rats induced cystitis, e.g. detrusor hyperreflexia and increased vascular permeability. Detrusor hyperreflexia was also observed in rats desensitized to capsaicin as adults (50-125 mg/kg s.c., 4 days before) but only for a short period (1 h) after instillation. When a longer time lag (24 h) was allowed to elapse following instillation, reflex micturition was almost abolished. In rats desensitized to capsaicin as newborns (50 mg/kg s.c. on second day of life) reflex micturition was almost abolished and xylene (given 1 h before measurement) was ineffective. The xylene-induced plasma extravasation was greater in the bladder neck than in the dome. In the bladder neck the "early" response to xylene was reduced but not abolished in rats densensitized to capsaicin as adults or pretreated with compound 48/80 and was abolished in rats desensitized to capsaicin as newborns. The bladder content of substance P-like immunoreactivity decreased at various times following xylene instillation but this change occurred in parallel to the increase in bladder weight. These findings indicate that xylene-induced cystitis involves, at least in part, an irritation of capsaicin-sensitive sensory nerves in the bladder wall. The present results further suggest that xylene acts by stimulating at least two populations of sensory nerves which differ in their sensitivity towards capsaicin.

Animals↗