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Biomedical subjects

C A Maggi

Publications and source records attributed to C A Maggi.

At least 487 records · Page 27Linked to original sources
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↗
PubMed1988

Further studies on the role of the adrenals in the capsaicin-sensitive "gastric defence mechanism".

Adrenalectomy enhances the degree of gastric ulcers induced in rats by indomethacin or acetylsalicylic acid (ASA), but not that induced by 96% ethanol. Systemic capsaicin pretreatment, which selectively induces degeneration of primary sensory neurons, produces aggravation of gastric ulcers induced by ASA, indomethacin or 96% ethanol in sham-operated animals but not in adrenalectomized rats. These findings provide evidence for the involvement of adrenal glands in the capsaicin-sensitive "gastric defence mechanism" regardless of the ulcerogenic stimulus used.

Adrenal Glands↗
PubMed1987

Involvement of a peripheral site of action in the early phase of neuropeptide depletion following capsaicin desensitization.

Levels of substance P-like immunoreactivity (SP-LI) of the rat urinary bladder were unaffected up to 1 h from exposure to capsaicin (1 microM) in vitro. A longer (3-6 h) exposure to capsaicin decreased SP-LI by about 40-60% as compared to 10-20% of controls. An analysis of the time course of bladder SP-LI changes following s.c. capsaicin (50 mg/kg) or extrinsic bladder denervation (pelvic ganglionectomy) indicated that at 3 h from capsaicin administration bladder SP-LI was reduced at an extent similar to that observed following in vitro exposure to the drug. These findings provide evidence that the early phase of tissue depletion of sensory neuropeptides following systemic capsaicin desensitization may involve a peripheral site of action.

Animals↗
PubMed1987

Visceromotor responses to calcitonin gene-related peptide (CGRP) in the rat lower urinary tract: evidence for a transmitter role in the capsaicin-sensitive nerves of the ureter.

Either intra-arterial or topical administration of calcitonin gene-related peptide (CGRP) had little effect on motility of the urinary bladder in urethane-anaesthetized rats. Only a high concentration (50 microM) of topical CGRP activated the micturition reflex and potentiated the response to exogenous substance P (SP). In the isolated rat bladder CGRP had inconsistent effects on spontaneous or field-stimulated contractions. CGRP neither produced any significant plasma extravasation (Evans blue leakage) in the rat lower urinary tract, nor potentiated the response to exogenous SP. CGRP inhibited motility in the rat isolated proximal urethra and ureters and counteracted the contractile response to neurokinins. An inhibitory effect of capsaicin on stimulated motility of the urethra was observed in all preparations and a small contractile response was evident in about 40% of cases. Lack of desensitization to the action of CGRP prevented the study of its interaction with capsaicin. The inhibitory effect of CGRP in the ureter exhibited a specific desensitization: if the preparations were pre-exposed to exogenous CGRP, the inhibition of motility produced by antidromic activation of the capsaicin-sensitive nerve terminals (field stimulation) as well as the response to capsaicin (1 microM) was prevented but the inhibitory response to isoprenaline was unaffected. These findings indicate that CGRP is able to influence markedly the motility of the rat lower urinary tract, but exhibits marked regional differences in its action. Endogenous CGRP could be the inhibitory transmitter which, when released from capsaicin-sensitive fibers, participate in the control of ureteral motility.

Animals↗
PubMed1987

Galanin: a potent modulator of excitatory neurotransmission in the human urinary bladder.

Galanin (GAL) produced a concentration (0.3-100 nM)-related inhibition of the atropine-sensitive component of the contractions induced by field stimulation of detrusor strips from the dome of the human urinary bladder. GAL had an ED50 of 2 nM for the inhibition. The effect of GAL was prevented by atropine (1 microM) and was not seen when the strips were stimulated with a cholinomimetic or KCl. These data suggest a possible neuromodulator role of GAL in the human urinary bladder.

Aged↗
PubMed1987

Exposure to calcium-free medium protects sensory fibers by capsaicin desensitization.

Capsaicin (1 microM) produces a tetrodotoxin-resistant contraction of the rat isolated urinary bladder ascribable to neuropeptide release from sensory nerves. A second application of capsaicin (1-10 microM) up to 5 h from the first one was ineffective, indicating complete desensitization. However, if the first exposure to capsaicin was made after a prolonged incubation in a Ca-free medium containing EDTA (0.1 mM), a second application of capsaicin (1 microM) was still able to induce a contraction, thus indicating protection from desensitization.

Animals↗
PubMed1987

Distribution of capsaicin-sensitive urinary bladder afferents in the rat spinal cord.

The capsaicin-sensitive afferent innervation of the urinary bladder and the central nervous system distribution of urinary bladder afferents have been studied in the rat. Capsaicin-sensitive primary sensory neurones supplying the urinary bladder have been found in two groups of spinal ganglia located in the Th13-L2 and L6-S1 segments. Capsaicin-sensitive primary sensory afferents from the bladder terminate within Rexed's laminae I, V and X, and in the dorsal gray commissure of the lumbosacral spinal cord. In addition, the results point to a possible vagal sensory innervation of the urinary bladder.

Afferent Pathways↗
PubMed1987

Immunoblockade of response to capsaicin in the rat vas deferens: evidence for the involvement of endogenous calcitonin gene-related peptide.

In the rat isolated vas deferens, capsaicin induced a transitory inhibition of the nerve-mediated contractions. This effect was not observed in preparations excised from capsaicin-pretreated rats nor following a first exposure to a high concentration of capsaicin in vitro. Exogenous calcitonin gene-related peptide (CGRP) induced a concentration-related inhibition of the nerve-mediated contractions. A highly avid and specific anti-CGRP serum raised in rabbits against conjugated synthetic rat CGRP inhibited selectively the capsaicin effect. These findings are consistent with the hypothesis that, in this preparation, the specific visceromotor response to capsaicin is brought about by the release of endogenous CGRP from sensory nerves.

Animals↗
PubMed1987

The contribution of capsaicin-sensitive innervation to activation of the spinal vesico-vesical reflex in rats: relationship between substance P levels in the urinary bladder and the sensory-efferent function of capsaicin-sensitive sensory neurons.

In acute spinal rats (C2-C3) the transvesical infusion of saline activates a vesico-vesical excitatory reflex (Brain Res., 380 (1986) 83-93). In bladders containing a subthreshold amount of fluid the topical application of capsaicin on the outer surface of the bladder dome activated this spinal reflex and also produced a transient rise in blood pressure and heart rate. The effects of systemic capsaicin desensitization (50 mg/kg s.c. 5 min, 60 days before) on the sensory (activation of the spinal vesico-vesical reflex) and 'efferent' (tetrodotoxin-insensitive capsaicin-induced contraction) functions mediated by the capsaicin-sensitive sensory fibers were correlated to changes in substance P-like immunoreactivity (SP-LI) content of the urinary bladder in adult rats. Blockade of both sensory and efferent functions was observed at a time (60 min from capsaicin administration) when the SP-LI content of the urinary bladder was unaffected. Four days after capsaicin desensitization the SP-LI levels of the bladder are almost depleted indicating that the neuropeptide(s) are entirely stored in sensory structures. At this time the sensory-efferent functions mediated by these fibers are still blocked. At 15-60 days from systemic capsaicin desensitization there was a progressive, time-related recovery of SP-LI levels in the bladder as well as of the sensory-efferent functions. These findings indicate a role of the capsaicin-sensitive innervation of the urinary bladder in activating the spinal vesico-vesical reflex. The present findings suggest that measurement of SP-LI levels in the rat bladder may be a useful biochemical index for monitoring the function(s) of the capsaicin-sensitive, peptidergic sensory neurons.

Animals↗
PubMed1987

The correlation between sensory-efferent functions mediated by the capsaicin-sensitive neurons and substance P content of the rat urinary bladder.

The substance P-like immunoreactivity (SP-LI) of the urinary bladder of adult rats was depleted by capsaicin desensitization (50 mg/kg, s.c., 4 days before) or extrinsic denervation (pelvic ganglionectomy) thus indicating its neurogenic sensory origin. SP-LI levels were inversely proportional to the volume threshold for micturition but not to the amplitude of micturition contraction. Moreover SP-LI levels were directly related to the amplitude of the capsaicin- but not field stimulation-induced contraction of the rat isolated bladder. These findings indicate that the SP-LI level of the rat bladder is a useful index for monitoring the dual sensory-efferent functions of the capsaicin-sensitive innervation of this organ.

Animals↗
PubMed1987

Further studies on the mechanisms of the tachykinin-induced activation of micturition reflex in rats: evidence for the involvement of the capsaicin-sensitive bladder mechanoreceptors.

The relative ability of substance P, neurokinin A, neurokinin B and kassinin to activate the micturition reflex was investigated in urethane-anaesthetized rats. When administered topically neurokinin A, neurokinin B and kassinin were 14, 36 and 280 times, respectively, more potent than substance P to activate micturition. On the other hand substance P, neurokinin A and kassinin were practically equipotent (and neurokinin B was about 3-4 times less potent than substance P) to stimulate the contraction of the rat isolated bladder and to potentiate the contractions induced by electrical field stimulation. This indicates that neither a direct action on muscle cells nor a potentiating effect on efferent neurotransmission can account for the rank order of potency of tachykinins for activation of the micturition reflex. The ability of topical tachykinins to activate the micturition reflex was largely impaired in 2 months old rats pretreated with capsaicin (50 mg/kg s.c.) on their second day of life, indicating that integrity of the capsaicin-sensitive bladder mechanoreceptors is essential for the production of this effect. These findings indicate that an NK-B receptor, possibly located on sensory nerves in the bladder wall, participates in the tachykinin-induced activation of reflex micturition.

Aging↗
PubMed1987

The effects of baclofen on spinal and supraspinal micturition reflexes in rats.

1. The effect of (+/-)-baclofen on micturition reflexes was investigated in urethane-anaesthetized rats. A 'low' dose of (+/-)-baclofen (0.5 mg/kg i.v.) barely affected the early phase of the transurethral cystometrogram (CMG) which involves activation of a spinal vesico-vesical excitatory reflex. 2. At a higher dose (2.5 mg/kg i.v.) (+/-)-baclofen suppressed both the spinal and supraspinal components of the bladder response to transurethral saline filling. 3. When the bladder was filled by the transvesical route a series of regular voiding cycles was obtained which are due to activation of a supraspinal vesico-vesical excitatory reflex. In this model, voiding efficiency of the rat bladder was markedly reduced even after a low dose of (+/-)-baclofen (0.5 mg/kg) and almost suppressed at 2.5 mg/kg. 4. (+/)-Baclofen reduction of voiding efficiency was mainly ascribable to an inhibitory effect on the expulsive phase of the voiding cycle which, in rats, depends critically upon the activation of a reflex which induces a twitch-like contraction of urethral/periurethral skeletal muscles. 5. (+/-)-Baclofen produced a small inhibition of the pinching-induced somatovesical excitatory reflex. (+/-)-Baclofen (2.5 mg/kg i.v.) produced also a marked but transient inhibition of bladder contractions induced by preganglionic nerve stimulation. However the time course of this effect was markedly shorter as compared to the long lasting suppression of voiding cycle observed with this same dose of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Regional differences in the effects of capsaicin and tachykinins on motor activity and vascular permeability of the rat lower urinary tract.

The effects of capsaicin, substance P (SP) and neurokinin A (NKA) on motor activity and vascular permeability was investigated in the rat lower urinary tract (bladder dome and neck, proximal urethra and ureters). Capsaicin produced contractions of the rat bladder dome and neck and of the proximal urethra in vitro, which were unaffected by tetrodotoxin and abolished by ganglionectomy. SP and NKA were almost equipotent in producing a contraction of the rat isolated bladder dome or neck and urethra. However, the maximal response to NKA was about twice that of SP on the urethra and bladder neck. Capsaicin did not affect motility of the unstimulated rat isolated ureter, while NKA or SP activated rhythmic contractions, NKA being about 850 times more potent than SP. Either capsaicin or field stimulation produced a transient inhibition of the NKA-activated rhythmic contractions of the rat isolated ureter which was prevented by capsaicin-desensitization. The capsaicin-(1 microM) or field stimulation-induced inhibition of NKA-activated rhythmic contractions of the rat isolated ureter were unaffected by removal of pelvic ganglia but abolished by cold storage (72 h at 4 degrees C). Intravenous capsaicin induced an inflammatory response (Evans blue leakage) in the bladder, proximal urethra and ureters in vivo. Plasma extravasation was greater in the ureters, urethra and bladder neck than in the dome. SP, NKA and histamine produced a dose-dependent dye leakage in all segments of the rat urinary tract, the response being slightly greater in the bladder neck than in the dome. The capsaicin-induced inflammatory response was abolished by systemic capsaicin-desensitization and reduced, to a variable extent, by pelvic ganglionectomy, in the various tissues examined. Topical application of tetrodotoxin on the bladder dome failed to affect the capsaicin-induced plasma extravasation in the urinary bladder. These findings indicate that chemoceptive, capsaicin-sensitive nerves are present throughout the whole rat lower urinary tract and their activation determines a variety of visceromotor responses and an increase of vascular permeability. In various instances the response to capsaicin may be explained by the action of tachykinins but some effects may involve other sensory neuropeptides.

Animals↗
PubMed1987

Cystometric changes in the early phase of streptozotocin-induced diabetes in rats: evidence for sensory changes not correlated to diabetic neuropathy.

The effect of streptozotocin (STZ) induced diabetes on rat urinary bladder function was investigated by means of 'in vivo' cystometry and 'in vitro' recording of bladder strips contractility. A group of sucrose-fed animals was included to determine to what extent the STZ-induced changes were ascribable to the increased diuresis. After 7-9 weeks from STZ injection there was a marked increase in weight of bladder and ureters. Cystometry revealed a marked increase in bladder capacity (volume threshold) although pressure threshold and amplitude of micturition contraction were unaffected. Sucrose-fed animals, having normal blood glucose levels but a similar increase in urine production exhibited cystometric changes identical to those of STZ animals. 'In vitro' experiments indicated that the response to field stimulation (0.1-20 Hz) is reduced in STZ-pretreated but increased in sucrose-fed animals, as compared to controls. The content of urinary bladder and ureters in sensory neuropeptides (substance-P, neurokinin-A and calcitonin-gene related peptide-like immunoreactivity) was increased by STZ diabetes when values were corrected for the increased weight of these organs. The capsaicin-induced contraction of the rat isolated bladder strips, presumably caused by neuropeptides released from intramural sensory nerves, is unaffected by STZ diabetes. These findings indicate that STZ diabetes produces, at an early stage, changes similar to those reported to occur in the human disease, e.g. a greater bladder capacity with unimpaired voiding function. The increased bladder capacity of STZ-rats seems largely, if not solely, ascribable to changes in physical properties of the detrusor muscle, thereby allowing accommodation of greater than normal volumes with similar increase of intraluminal pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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

Species-related variations in the effects of capsaicin on urinary bladder functions: relation to bladder content of substance P-like immunoreactivity.

1. The effect of capsaicin on bladder motility in vivo (urethane anaesthesia) and in vitro, plasma extravasation (Evans blue leakage technique) and content of substance P-like immunoreactivity (SP-LI) of the urinary bladder was investigated in various mammalian species. 2. Systemic capsaicin desensitization (rat and hamster, 50 mg/kg s.c. 4 days before; guinea-pig 55 mg/kg s.c. 4-7 days before) increased bladder capacity in rats and guinea-pigs and reduced voiding efficiency in guinea-pigs. All other urodynamic parameters were unaffected in both rats, guinea-pigs and hamsters. 3. Reflex bladder voiding was abolished by spinal cord transection in anaesthetized rats and hamsters. On the other hand, hexamethonium-(20 mg/kg i.v.)sensitive voiding contractions were obtained in response to saline filling 45 min from cord transection in guinea-pigs, indicating a profound interspecies variation in the basic organization of micturition. 4. Exposure to capsaicin (1 microM) produced a contraction of the isolated bladder from rats, guinea-pigs (dome) and mice. Capsaicin produced only a slight contractile response in the guinea-pig bladder base. The motor response to capsaicin of the rat, guinea-pig and mouse bladder exhibited marked desensitization, suggesting a specific effect on sensory nerves. On the other hand, capsaicin (1 microM) produced a slight relaxation of the hamster isolated bladder but this effect was reproducible at 1-2 h intervals, suggesting an unspecific effect. Capsaicin (1-10 microM) did not affect motility of strips from the dome or the base of the rabbit bladder. 5. Intravenously administered capsaicin produced a marked plasma extravasation (Evans blue leakage) in the lower urinary tract of rats, mice and guinea pigs. In rats but not guinea-pigs the reaction in the bladder base was greater than in the dome. In hamsters intravenous capsaicin failed to induce any significant Evans blue leakage in the lower urinary tract. 6. SP-LI was detected in the lower urinary tract of rats, guinea-pigs, rabbits and mice but not hamsters. Bladder SP-LI was depleted by systemic capsaicin desensitization in rats, guinea-pigs and mice. Reverse phase HPLC indicated that all the immunoreactive material co-eluted with authentic substance P or its oxidized form. 7. These findings indicate that noticeable species-related differences exist with regard to the functions mediated by the capsaicin-sensitive neurons in the urinary bladder.

Animals↗
PubMed1987

Substance P-like immunoreactivity in capsaicin-sensitive structures of the rat thymus.

Unlike in mouse and hamster, the thymus of rats or guinea pigs contains measurable amounts of substance P-like immunoreactivity (SP-LI), which, in a HPLC system, eluted as authentic SP or SP sulfoxide. Ontogenetic study showed that in rats the SP-LI content of the thymus increased up to 60 days from birth, and decreased thereafter. Capsaicin, but not 6-hydroxydopamine (6-OHDA) pretreatment completely depleted thymic SP-LI content in both newborn and adult rats. Animals treated with capsaicin as newborns, but not as adults, showed lower thymus weights as compared to controls. Rats pretreated with capsaicin as adults underwent partial time-dependent recovery of thymic SP-LI content. Somatostatin-like immunoreactivity (SST-LI) of rat thymus, eluting in part as authentic SST, was unaffected both by capsaicin or 6-OHDA pretreatment. Taken together, these findings demonstrate the existence of capsaicin-sensitive structures containing SP in the rat thymus. The possible function(s) that capsaicin-sensitive structures could exert in the thymus, among which a trophic action, mediated by the efferent function of sensory neurons, remain(s) to be established.

Aging↗