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Biomedical subjects

C A Maggi

Publications and source records attributed to C A Maggi.

At least 469 records · Page 26Linked to original sources
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

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

Capsaicin-sensitive tachykinin-like immunoreactivity in the thymus of rats and guinea-pigs.

Capsaicin-sensitive, substance P-like immunoreactivity (SP-LI) has been detected recently in rat thymus. Other tachykinins are frequently present with SP. In the present study, tachykinin-like immunoreactivity (TK-LI) was measured in guinea-pig, rat, mouse and hamster thymus with the amount detectable being greatest in guinea-pig, less in rat and least in mouse; it was not detectable in hamsters. In guinea-pig and rat thymus, but not in mouse, TK-LI was markedly reduced by pretreatment with capsaicin. TK-LI levels correlated significantly with those of SP-LI in both guinea-pig and rat thymus. High-performance liquid chromatography (HPLC) fractions considered to represent neurokinin A, eledoisin and neuropeptide K were present in guinea-pig thymus but only the first two were present in rat thymus.

Animals↗
PubMed1988

Distribution of calcitonin gene-related peptide-like immunoreactivity in various rat tissues: correlation with substance P and other tachykinins and sensitivity to capsaicin.

Calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) has been measured in various tissues of control rats and rats pretreated with systemic capsaicin, s.c. (50 mg/kg as newborns or as adults, 125 mg/kg as adults) and compared with the tissue level of substance P- and tachykinin-like immunoreactivities (SP-LI and TK-LI). The rank order of CGRP-LI concentration in various tissues was as follows: trigeminal ganglion greater than urinary bladder greater than ureter much greater than distal duodenum much greater than proximal duodenum much greater than skin (snout) greater than thymus = right atrium = vas deferens. A complete depletion of CGRP-LI following capsaicin treatment of both adult and newborn animals was observed in urinary bladder, ureter, atrium, vas deferens and skin. Capsaicin pretreatment of both adult and newborn rats reduced CGRP-LI in the duodenum by about 50%. CGRP-LI in trigeminal ganglion was reduced only in newborn animals, while it was not affected in the thymus. The CGRP-LI/SO-LI ratio varied in these tissues between 33.2 (urinary bladder) and 0.9 (proximal duodenum). A significant correlation was found between CGRP-LI and SP-LI or TK-LI in tissues where immunoreactivities were depleted by capsaicin, as well as in the urinary bladder of individual animals. The correlation between CGRP-LI with SP-LI and TK-LI upon treatment with capsaicin indicates that neurons containing SP and TK as well as CGRP, and neurons containing CGRP only, are affected in a similar manner by capsaicin.

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↗
PubMed1988

Regional differences in the motor response to capsaicin in the guinea-pig urinary bladder: relative role of pre- and postjunctional factors related to neuropeptide-containing sensory nerves.

Capsaicin induced a contraction of isolated strips from the guinea-pig urinary bladder which was more evident in the dome than in the neck and inhibited contractions induced by field stimulation, particularly in the neck. Both responses exhibited prompt desensitization and were tetrodotoxin-resistant, suggesting a specific action on transmitter release from sensory nerve terminals. Indeed, the contractile response in the dome was prevented by a substance P antagonist while the inhibitory response in the neck was prevented by immunoblockade with anticalcitonin gene-related peptide (CGRP) serum. Substance P produced a contraction of the guinea-pig bladder, being about 5 times more potent in the dome than in the neck, while CGRP inhibited the evoked contractions, being about 8 times more potent in the neck than in the dome. Further, the maximal effect of CGRP in the neck was almost double that in the dome. Substance P- and CGRP-like immunoreactivity were detected in both the dome and the neck with no regional differences for each peptide. CGRP-like immunoreactivity was 6.3 and 7.9 times higher than substance P-like immunoreactivity in the dome and the neck, respectively. Exposure to capsaicin evoked release of both substance P- and CGRP-like immunoreactivity from the dome and the neck. Peak CGRP-like immunoreactivity released by capsaicin was 12.3 and 8 times greater than substance P-like immunoreactivity in the dome and the neck, respectively. For each peptide, no difference was found in peak release in the dome vs neck. Total substance P-like immunoreactivity released from the neck was 25% lower than that released from the dome. The ability of CGRP to stimulate accumulation of 3',5' cyclic adenosine monophosphate in membranes prepared from the bladder muscle was greater in preparations from the neck than from the dome. These findings indicate that postjunctional mechanisms (type and number of receptors for sensory neuropeptides, coupling with second messengers) are a major determinant of the type of motor responses consequent of the release of sensory neuropeptides from capsaicin-sensitive nerves.

Animals↗
PubMed1988

Secretion, pain and sneezing induced by the application of capsaicin to the nasal mucosa in man.

1. Topical application of capsaicin to the human nasal mucosa induced a burning sensation and sneezing. A dose-dependent seromucous nasal secretion was also observed. Capsaicin (75 micrograms) was more potent than methacholine (50 mg) in producing nasal secretion, while topical histamine (200 micrograms), substance P (135 micrograms) and calcitonin gene-related peptide (36 micrograms) did not induce rhinorrhea. 2. Pretreatment with either topical ipratropium bromide, systemic dexchlorpheniramine or indomethacin did not influence the effects induced by capsaicin. Topical pretreatment with lidocaine inhibited the painful sensation but failed to block the rhinorrhea. Desensitization to the effects of capsaicin occurred following 4-5 subsequent applications, and full recovery was observed within 30-40 days. 3. It is proposed that the effects of capsaicin in human nasal mucosa are due to excitation of primary afferent neurones that (a) convey burning and painful sensation, (b) evoke a sneezing reflex and (c) induce nasal secretion by releasing transmitter(s) from their peripheral terminals.

Administration, Intranasal↗
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

GABAA receptor sites modulating catecholamine secretion in the rat adrenal gland: evidence from 3H-muscimol autoradiography and in vivo functional studies.

The occurrence and distribution of specific 3H-muscimol binding sites, most probably identical with A type gamma-aminobutyric acid (GABA) receptors, were studied in sections of the rat adrenal gland by light microscope autoradiography. Specific binding was found primarily in the adrenal medulla, in association with chromaffin cells. A limited number of binding sites was also observed within the adrenal cortex. In urethane-anaesthetized hexamethonium-pretreated rats, intravenous GABA produced a set of 'excitatory' cardiovascular effects (increase in heart rate, force of contraction and blood pressure) which were mimicked by intravenous muscimol but not by intravenous baclofen, and were antagonized by pretreatment with bicuculline. The cardiovascular excitatory effects of intravenous GABA were unaffected by reserpine pretreatment, markedly reduced by administration of phentolamine plus propranolol, and almost completely abolished by adrenalectomy. Our findings indicate the presence of GABA receptor sites on adrenal chromaffin cells, whose excitation can produce changes in cardiovascular function.

Adrenal Cortex↗
PubMed1988

Neurokinin receptors in the rat lower urinary tract.

The effects of neurokinins (NKs), tachykinins and some NK-related peptides (selective agonists for the NK-1, NK-2 or NK-3 receptors) have been investigated in the various sections of the rat lower urinary tract. In the isolated bladder, all peptides were substantially equipotent with the exception of senktide, an NK-3 agonist, which was distinctly less potent than the other compounds. Similar results were obtained in the isolated urethra. In these tissues, the maximal response to NK-1 agonists was distinctly less intense than that to the other peptides. In the bladder, exposure to phenoxybenzamine (30 microM for 90 min) reduced the response to NK-A but not that to substance P, KCl or field stimulation. In the isolated ureter, peptides active at both the NK-2 and the NK-3 sites [including senktide and [MePhe7]-NKB(4-10)] activated, at nanomolar concentrations a series of rhythmic contractions, whereas peptides active at the NK-1 site, were active only at micromolar concentrations. These findings provide further evidence that multiple NK receptors are present in the rat lower urinary tract. In the bladder, NK-2 and NK-1 sites mediate the direct response to NKs, in accordance with binding and autoradiographic data. In the ureter, both NK-2 and NK-3 sites may activate the direct contractile response to these substances.

Animals↗
PubMed1988

Neurokinins induce a relaxation of the rat duodenum "in vivo" by activating postganglionic sympathetic elements in prevertebral ganglia: involvement of an NK-2 type of neurokinin receptor.

In the small intestine of urethane-anesthetized rats, i.v. neurokinins (NKs) (0.043-14 nmol/kg) produce three distinct motor effects, e.g.: 1) a transient relaxation followed by 2) a phasic contraction and 3) a tonic contraction. The aim of this study was to characterize the nature of the receptor determining the transient relaxation and mechanisms involved. The transient relaxation was more evident in the distal than in the proximal duodenum or in the jejunum. The rank order of potency of NKs in producing relaxation was NKA greater than substance P greater than NKB. The heptapeptide NKA(4-10) was as potent as the decapeptide NKA in determining relaxation but less potent than NKA in producing phasic or tonic contraction. NKA (0.43 nmol/kg i.v.)-induced relaxation and tonic contraction were unaffected by [D-Pro2, D-Trp7.g]substance P, a compound which, in this tissue, acts as a NK-1 receptor antagonist. NKA (0.43 nmol/kg i.v.)-induced relaxation of the distal duodenum was unaffected by atropine, hexamethonium or adrenalectomy, reduced by phentolamine plus propranolol and abolished by guanethidine or acute (15 min before) removal of the celiac ganglion complex. These findings are consistent with the hypothesis that activation of a NK-2 receptor located on postganglionic sympathetic neurons in the prevertebral ganglia produces the intestinal relaxation in response to i.v. NKs.

Adrenalectomy↗