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Biomedical subjects

A Meli

Publications and source records attributed to A Meli.

At least 145 records · Page 8Linked to original sources
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

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

Lack of relationship between effect of desipramine on forced swimming test and brain levels of desipramine or its demethylated metabolite in rats.

Animals were injected with 20 mg/kg desipramine (DMI) 1 h (acute) or 24, 5 and 1 h (subchronic) or once daily for 7 consecutive days (chronic) before the forced swimming test (FST). DMI was also injected at a dose of 40 mg/kg acutely. Animals were killed immediately after test for evaluation of brain concentrations of DMI and its demethylated metabolite desmethyldesipramine (DDMI). Acute and chronic DMI 20 mg/kg gave rise to similar brain concentrations but only chronic DMI was active on FST. Acute DMI 20 mg/kg and 40 mg/kg gave rise to different brain concentrations but similar effects on FST. DDMI concentrations were similar after the various DMI treatments. Results seem to indicate that no relationship exists between effect of DMI on FST and brain concentrations of either DMI or DDMI.

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↗
PubMed1987

Motor activity of the rat duodenum in vivo: evidence for the existence of an atropine-resistant peristalsis.

The motor activity of the proximal duodenum has been investigated by means of a balloon method in urethane-anaesthetized rats. A series of atropine- (1 mg/kg i.v.) or hexamethonium- (20 mg/kg i.v.) sensitive rhythmic contractions can be demonstrated in the rat duodenum which represents a peristaltic reflex mediated by intramural cholinergic neurons. The atropine-sensitive peristaltic reflex is transiently suppressed by intravenous DMPP (0.1 mg/kg) GABA (3 mg/kg) or noradrenaline (10 micrograms/kg). In rats pretreated with guanethidine (20 mg/kg s.c.) plus naloxone (2 mg/kg i.v.) and theophylline (2 mg/kg i.v.) a second type of peristaltic reflex which is atropine-resistant but hexamethonium-sensitive can be demonstrated. These findings indicate that in the rat small intestine a peristaltic activity can be sustained by both atropine-sensitive and atropine-resistant mechanism, which may explain failure of atropine to affect intestinal motility in conscious rats.

Animals↗
PubMed1987

Influence of peripherally-administered peptides on ethanol-induced gastric ulcers in the rat.

1. Subcutaneous administration of bombesin (50-200 micrograms/kg), cholecystokinin-8 (10-100 micrograms/kg) and epidermal growth factor (10-100 micrograms/kg) but not calcitonin gene-related peptide (25 micrograms/kg), neurotensin (500 micrograms/kg) or substance P (200 micrograms/kg) produced a marked and dose-related inhibition of ethanol-induced gastric lesions in rats. 2. These actions were inhibited by a non-ulcerogenic dose of indomethacin suggesting that prostaglandins are involved in the protective activity of bombesin, cholecystokinin-8 and epidermal growth factor.

Animals↗
PubMed1987

Anti-ulcer activity of calcitonin gene-related peptide in rats.

Calcitonin gene-related peptide (CGRP, 5-10 micrograms/kg s.c.). reduced both incidence and degree of indomethacin- or acetylsalicylic acid (ASA) plus HCl-induced gastric as well as cysteamine-induced duodenal ulcers in rats. CGRP had no effect on ethanol-induced gastric lesions. The anti-ulcer activity of CGRP is most likely ascribable to its potent antisecretory properties.

Animals↗
PubMed1987

Peripheral effects of neurokinins: functional evidence for the existence of multiple receptors.

The ability of six neurokinins (substance P, neurokinin A, neurokinin B, physalaemin, eledoisin and kassinin) to induce hypotension, salivary secretion and to activate motility of the duodenum and of the urinary bladder was investigated in urethane-anaesthetized rats. A comparison of the relative potency of these substances in producing a given biological effect yielded results consistent with the hypothesis of the existence of three distinct types of receptor in rat peripheral tissues, namely SP-P, SP-K and SP-E according to the nomenclature proposed by Buck, Burcher, Shults, Lovenberg & O'Donohue (1984), or NK-P, NK-A and NK-B according to that of Regoli, D'Orleans-Juste, Drapeau, Dion & Escher (1985). An NK-P receptor is responsible for the production of the hypotensive effect and for the activation of salivary secretion. An 'NK-P like' receptor subtype may be involved in determining the direct contractile effects on muscle cells of neurokinins in the rat isolated urinary bladder and the 'phasic' contraction of the rat duodenum. An NK-A receptor mediates the 'tonic' contraction of the rat duodenum while an NK-B receptor mediates the activation of the micturition reflex. Evidence is presented that multiple neurokinin receptors are present in the same organ and participate with different modalities to the regulation of smooth muscle function.

Animals↗
PubMed1987

Capsaicin-induced inhibition of motility of the rat isolated vas deferens: do multiple neuropeptides mediate the visceromotor effects of capsaicin?

1 The effects of capsaicin have been investigated in the field-stimulated (0.1 Hz) or unstimulated rat isolated vas deferens and compared with those of some neuropeptides (neurokinins, calcitonin gene-related peptide (CGRP) putatively stored in capsaicin-sensitive sensory fibres. 2 Capsaicin (0.01-3 microM) produced a concentration-related transient inhibition of the field-stimulation-induced twitches. This effect was characterized by marked desensitization and could not be elicited in preparations excised from capsaicin-pretreated rats (50 mg/kg s.c., 4 days before). The amplitude of the nerve-mediated twitches was unaffected by capsaicin-desensitization. 3 Neurokinins (substance P, Kassinin) produced a potentiation of the nerve-mediated contractions while CGRP had a potent inhibitory effect. In the presence of Kassinin, CGRP still inhibited twitches although the time course of this inhibitory effect was delayed as compared to controls. 4 In the unstimulated rat vas deferens neither capsaicin (3 microM) nor CGRP (0.1 microM) had any significant motor effect. However, when phasic contractions were initiated by previous exposure to Kassinin (0.2 microM), both capsaicin (3 microM) or CGRP (10-100 nM) had a prompt inhibitory effect. Capsaicin inhibition exhibited a marked desensitization while the effect of CGRP was still evident after capsaicin-desensitization. 5 The inhibitory effect of capsaicin or CGRP on the Kassinin-stimulated rhythmic contractions of the rat isolated vas deferens was unaffected by a previous exposure to tetrodotoxin (0.5 microM). 6 Storage at 4 degrees C for 24 h produced a 65% reduction of the response of the rat isolated vas deferens to nerve-stimulation. The residual response was tetrodotoxin-sensitive and could be potentiated by Kassinin (0.2 microM) or inhibited by CGRP (10-100 nM) as observed in controls. In these preparations the inhibitory effect of capsaicin (3 microM) was significantly reduced (approximately equal to 50%) and in some preparations abolished, as compared to controls. 7 These findings indicate the existence, in the rat isolated vas deferens, of capsaicin-sensitive sensory innervation which, upon chemical stimulation, releases, through a tetrodotoxin-insensitive mechanism, a substance(s) which inhibits motility at postjunctional level. CGRP is a possible candidate for the role of inhibitory sensory transmitter released from capsaicin-sensitive nerve endings in this preparation.

Animals↗
PubMed1987

Neuroeffector mechanisms in the voiding cycle of the guinea-pig urinary bladder.

1. The effect of drugs expected to modify cholinergic (atropine, physostigmine) or GABA-ergic (GABA, picrotoxin, bicuculline methiodide, BMI) neurotransmission were investigated on the voiding cycle of the urinary bladder in urethane-anaesthetized guinea-pigs. 2. Transvesical saline infusion elicited a series of regular voiding cycles which were abolished by topical tetrodotoxin as well as by topical or intravenous (i.v.) hexamethonium, thus indicating their reflex neurogenic origin. 3. Either i.v. or topical atropine decreased amplitude and duration of micturition contraction, reduced efficiency of bladder voiding and, in about 30% of preparations, suppressed micturition (overflow incontinence). Either topical or i.v. physostigmine potentiated, in an atropine-sensitive manner, voiding efficiency. 4. GABA was administered during the ascending limb of the voiding cycle: i.v. GABA inhibited while topical GABA increased efficiency of the first voiding cycle. Both direction and intensity of the effect of GABA were dependent upon initial pressures. The second and following voiding cycles after GABA administration were inhibited transiently. 5. Either topical or i.v. picrotoxin or BMI potentiated the efficiency of the voiding cycle of the guinea-pig bladder. In these preparations either i.v. or topical GABA (administered during the ascending limb of the voiding cycle) produced only inhibitory effects on voiding efficiency. 6. These findings indicate that, in guinea-pigs, bladder voiding is largely dependent upon an intact cholinergic neurotransmission. Although amplitude of the initial voiding contraction is largely atropine-resistant, its duration and, consequently, degree of bladder voiding, are strongly influenced by blockade (atropine) or potentiation (physostigmine) of cholinergic neurotransmission. Endogenous GABA-ergic mechanism modulate, possibly at peripheral level, the voiding efficiency of the guinea-pig bladder. GABA exerts a complex neuromodulatory influence on voiding function, its overall effect being mainly influenced by resting parameters.

Animals↗
PubMed1987

Four motor effects of capsaicin on guinea-pig distal colon.

The motor effects of capsaicin on the guinea-pig distal colon have been investigated in vivo and in vitro. Capsaicin (0.1-10 micrograms kg-1 i.v.) produced a transient relaxation which was reduced by pretreatment with capsaicin itself, atropine, hexamethonium, phentolamine or guanethidine and almost abolished by tetrodotoxin (TTX). Topically applied capsaicin produced a transient inhibition of tone and spontaneous activity prevented by topically applied TTX. In isolated preparations of distal colon, capsaicin produced a transient, TTX- and atropine-sensitive contraction which was followed by a depression of the contractile activity. The depressant effect was unaffected by atropine plus guanethidine but was greatly reduced by TTX, indicating activation of intramural non-adrenergic, non-cholinergic (NANC) mechanisms. The depressant effect on the first exposure to capsaicin (1 microM) was greater than that produced by a second, third or fourth exposure. In preparations excised from capsaicin-pretreated animals, capsaicin (1 microM) only produced an inhibitory effect on spontaneous contractions. Desensitization did not occur to this inhibitory effect. In preparations pre-exposed to capsaicin (1 microM, 1 h before), capsaicin (1-30 microM) produced a concentration-related inhibition of spontaneous contractions (IC50 = 19 microM) and of the high K+-induced tonic contraction (IC50 = 23 microM). A similar effect on spontaneous motility was produced by capsaicin in colonic segments excised from capsaicin-pretreated guinea-pigs (IC50 = 16 microM) or guinea-pigs treated with TTX (IC50 = 20 microM). It is concluded that, in vivo, capsaicin activates inhibitory reflexes, presumably due to stimulation of primary afferent fibres. This effect involves, at least in part, activation of sympathetic nerves to this organ. The contractile effect of capsaicin on the isolated colon involves activation of intramural cholinergic neurones, whereas the TTX-sensitive component of the inhibitory effect involves either release of an inhibitory transmitter through an axon reflex arrangement or activation of NANC neurones. In addition, at high concentrations capsaicin produces a direct depression of smooth muscle contraction.

Animals↗
PubMed1987

Capsaicin-sensitive mechanisms and experimentally induced duodenal ulcers in rats.

The incidence and degree of cysteamine- or dulcerozine-induced duodenal ulcers are increased by systemic capsaicin desensitization (50 mg kg-1 s.c. 4 days before) in adult rats. Acute administration of capsaicin, but not neurokinins or CGRP, produced a small but distinct plasma extravasation (Evans blue leakage) in the rat proximal duodenum which was absent in capsaicin-pretreated rats. These findings indicate the existence of a capsaicin-sensitive 'duodenal defence mechanism' in rats.

Animals↗
PubMed1987

The presence of mucosa reduces the contractile response of the guinea-pig urinary bladder to substance P.

The contractile response to substance P in-vitro is greater in strips of guinea-pig bladder freed of mucosa than in normal strips, while the response to field stimulation, histamine or KCl is unaffected by the presence of mucosa. Substance P has no inhibitory effect on histamine-induced contractions of the guinea-pig bladder. These findings support the possibility that the presence of mucosa may reduce accessibility of substance P to the muscle layer.

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↗
PubMed1987

Involvement of capsaicin-sensitive mechanism(s) in the antiulcer defence of intestinal mucosa in rats.

Capsaicin desensitization increases degree and incidence of indomethacin-induced intestinal ulcers in rats, suggesting the existence of a capsaicin-sensitive mechanism(s) in the protection of the intestinal mucosa against indomethacin-induced ulceration. Sensory innervation thus may be involved in the pathogenesis of ulcers of the small bowel, as well as in gastric ulcers. Administration of exogenous CGRP and somatostatin, sensory neuropeptides which are depleted by capsaicin desensitization, does not afford protection toward the capsaicin-induced aggravation of intestinal ulcers. The protective effect of exogenous prostaglandins toward indomethacin-induced intestinal ulceration is not mediated by capsaicin-sensitive nerve fibers.

Animals↗
PubMed1987

Evidence for the involvement of a capsaicin-sensitive innervation in the afferent branch of micturition reflex in rats.

Functional evidence is presented indicating the presence in the rat urinary bladder of a capsaicin-sensitive innervation which is involved in regulating micturition threshold. Endogenous substance P and/or related tachykinins appear to be present in the capsaicin-sensitive nerve endings of the rat bladder and may play a neurotransmitter role in relaying information concerned with bladder volume from the detrusor muscle to the central nervous system. In addition, neurotransmitter release from the peripheral ending of the capsaicin-sensitive fibers may play an efferent role in certain motor and/vascular responses at bladder muscle level.

Afferent Pathways↗
PubMed1987

Spinal and supraspinal components of GABAergic inhibition of the micturition reflex in rats.

The effect of gamma-aminobutyric acid (GABA)ergic drugs on micturition reflexes was investigated in urethane-anesthetized rats. Intracisternally administered GABA or homotaurine inhibited, in a bicuculline-sensitive manner, the supraspinal micturition reflex. Bicuculline or picrotoxin increased the amplitude and duration of the micturition contractions of supraspinal origin, suggesting the existence of a tonic GABAergic inhibitory mechanism. Neither diazepam nor bicuculline or picrotoxin had any significant effect on threshold of the spinal vesico-vesical micturition reflex. Aminooxyacetic acid, an inhibitor of GABA catabolism, increased threshold of the spinal but not of the supraspinal vesico-vesical reflex in a bicuculline-sensitive manner. Volume threshold for eliciting the supraspinal reflex was increased by diazepam and decreased by picrotoxin. Neither picrotoxin nor aminooxyacetic acid modified amplitude of bladder contractions elicited by pinching of the perineal skin (spinal somato-vesical reflex) nor of that produced by preganglionic nerve stimulation of the excitatory nerves. It is concluded that endogenous GABAergic mechanisms involving the activation of GABA A receptors modulate both the spinal and the supraspinal vesico-vesical micturition reflexes. These endogenous GABAergic mechanism(s) are operating tonically in inhibiting micturition at supraspinal but not spinal level.

Aminooxyacetic Acid↗