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Biomedical subjects

A Meli

Publications and source records attributed to A Meli.

At least 55 records · Page 3Linked to original sources
PubMed1989

The 'efferent' function of capsaicin-sensitive nerves: ruthenium red discriminates between different mechanisms of activation.

We have investigated the ability of Ruthenium Red, an inorganic dye with calcium entry blocking properties, to interfere with the 'efferent' function of capsaicin-sensitive sensory nerves. These nerves were activated in the guinea-pig isolated bronchus (atropine in the bath) or left atria (reserpine-pretreated animals, atropine in the bath) by electrical field stimulation or with capsaicin. Both stimuli produced a contraction of the bronchus and a positive inotropic response in the atria, responses which are mediated by endogenous neuropeptides (tachykinins in the bronchus, calcitonin gene-related peptide in the atria) released from sensory nerves. Ruthenium Red (10 microM for 20 min in both cases) selectively inhibited the responses produced by the administration of capsaicin, while leaving the responses to electrical field stimulation unaffected. Likewise, the bronchoconstrictor response to exogenous neurokinin A and the atrial positive inotropic response to calcitonin gene-related peptide were unaffected by Ruthenium Red. A prejunctional site of action of Ruthenium Red was confirmed in release experiments where the dye strongly inhibited the capsaicin-evoked outflow of calcitonin gene-related peptide, which is taken as a marker of activation in sensory nerves. Together with other observations, these findings support the concept that there are two independent mechanisms for activating the 'efferent' function of sensory nerves, one of which is activated by capsaicin and is Ruthenium Red-sensitive but omega-conotoxin-resistant, while the other is activated by propagated action potentials (field stimulation) and is omega-conotoxin-sensitive and Ruthenium Red-resistant.

Animals↗
PubMed1989

The hamster isolated trachea: a new preparation for studying NK-2 receptors.

Mammalian tachykinins (substance P, neurokinin A and neurokinin B) produced a concentration-related contraction of the hamster isolated trachea with the following order of potency: NKA congruent to NKB much greater than substance P (SP). NKA and NKB were 280 and 203 times more potent than SP, respectively. The action of NKA, NKB or SP was not significantly modified in presence of thiorphan (10 microM), atropine (1 microM), mepyramine (1 microM) or indomethacin (5 microM). [Nle10]NKA-(4-10) or [beta Ala8]NKA-(4-10), two selective NK-2 receptor agonists, displayed good activity while other synthetic agonists, selective for NK-1 or NK-3 receptors, had little or no effect. The contractile response to tachykinins did not undergo appreciable desensitization and was promptly reversed by washing out. These data indicate that NK-2 receptors are the main if not the sole mediators of the response of the hamster isolated trachea to tachykinins, whose action is independent from cholinergic nerves, histamine release or prostaglandin production. Further, no significant peptide degradation by a thiorphan-sensitive mechanism occurs in this organ.

Animals↗
PubMed1989

Effect of thiorphan on response of the guinea-pig gallbladder to tachykinins.

Tachykinins produced a concentration-related contraction of the isolated guinea-pig gallbladder, with a rank order of potency neurokinin A (NKA) greater than Arg-neurokinin B = neurokinin B (NKB) greater than substance P (SP). Only the effect of SP was potentiated by thiorphan (0.1-10 microM). A significant enhancement of the response to SP was also produced by captopril (1 microM). [Nle10]NKA-(4-10) and [beta-Ala8]NKA-(4-10), selective NK-2 receptor agonists, were active, whereas [Pro9]SP sulfone (selective NK-1 agonist) was almost ineffective. [MePhe7]NKB (selective NK-3 agonist) had some activity but only at high concentrations. Septide was almost ineffective and DiMeC7 had an action comparable to that of [MePhe7]NKB. None of the effects induced by these synthetic tachykinin analogs were significantly potentiated by thiorphan. Capsaicin (10 microM) produced a contraction which was unaffected by thiorphan. Both capsaicin and NKA-induced contractions were antagonized by Spantide at concentrations (5-10 microM) which had no effect against the atropine-sensitive contractions produced by electrical field stimulation. Capsaicin (1 microM) produced a consistent release of SP-like immunoreactivity (SP-LI) and a second application of the drug had no further effect, indicating complete desensitization. SP-LI release by capsaicin was almost doubled in the presence of thiorphan. These findings indicate that NK-2 and possibly some NK-3 receptors mediate the contractile response of the guinea-pig gallbladder to tachykinins. Both exogenous and endogenous (released by capsaicin) SP were degraded to a significant extent in this organ via a thiorphan-sensitive mechanism, the identity of which remains to be established.

Animals↗
PubMed1989

Duodenal ulcers are associated with a depletion of duodenal calcitonin gene-related peptide-like immunoreactivity in rats.

Calcitonin gene-related peptide-like immunoreactivity (CGRP-li) was decreased in duodenal samples from animals treated with ulcerogens such as dulcerozine, cysteamine or mepirizole. The degree of these experimental ulcers was inversely correlated with the levels of duodenal CGRP-li. These findings show that endogenous CGRP may play an important role in duodenal ulcerogenesis.

Animals↗
PubMed1989

Modulatory action of galanin on responses due to antidromic activation of peripheral terminals of capsaicin-sensitive sensory nerves.

Galanin inhibited, in a concentration-dependent manner (EC50 7.2 nM), the positive inotropic response produced by field stimulation of isolated left atria from reserpine-pretreated guinea-pigs (in the presence of atropine). These responses were shown to involve antidromic activation of capsaicin-sensitive primary afferents. On the other hand, galanin did not affect the inotropic response to capsaicin or calcitonin gene-related peptide, the putative endogenous mediator released from sensory nerves. Galanin-(1-10) was at least 10,000 times less potent than the parent peptide, while galanin-(25-29) was ineffective. Likewise, galanin inhibited the non-cholinergic contraction produced by field stimulation of the isolated guinea-pig bronchus but not the contraction produced by exogenous neurokinin A. These findings indicate a prejunctional neuromodulatory action of galanin on the excitability of peripheral terminals of capsaicin-sensitive sensory nerves.

Animals↗
PubMed1989

Release of VIP- but not CGRP-like immunoreactivity by capsaicin from the human isolated small intestine.

Exposure to capsaicin (1 microM) produced a prompt and sustained release of vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) from mucosa-free strips of human small intestine (jejunum and ileum). A second application of capsaicin, 60 min later, had no effect indicating complete desensitization, a specific feature of the action of capsaicin on sensory nerves. By contrast no release of calcitonin gene-related peptide (CGRP)-LI was produced upon the first or second application of capsaicin.

Aged↗
PubMed1989

Potent contractile effect of endothelin in isolated guinea-pig airways.

Endothelin produced a concentration-dependent (1 nM-0.3 microM) contraction of isolated guinea-pig airways (trachea and main bronchi). The response was unaffected by tetrodotoxin (1 microM) and slightly depressed by indomethacin (5 microM) but promptly abolished by isoprenaline (1 microM) or EDTA (3 mM). In the bronchi, the response to endothelin was enhanced by removal (rubbing) of the epithelium. The response of the trachea or bronchi to endothelin (0.3 microM) was unaffected by NiCl2 (0.1 mM) or omega conotoxin (0.1 microM) but was partially inhibited by nifedipine (1 microM).

Animals↗
PubMed1989

Conformationally constrained tachykinins: N-methylated analogues of neurokinin A.

Limited conformational constraints have been introduced in the sequence of the C-terminal fragment of the peptide neurotransmitter neurokinin A by N-methylation of individual peptide bonds, and the biological activities of the peptides thus obtained were evaluated in order to assess the effect of such conformational constraint on receptor selectivity. The analogue methylated in position 7 shows enhanced selectivity toward NK-1 receptor.

Amino Acid Sequence↗
PubMed1989

The motor response to ethylenediamine of the rat isolated duodenum: involvement of GABAergic transmission?

We have studied the motor response to ethylenediamine (EDA), a well known releaser of endogenous GABA, on the longitudinal muscle of the rat isolated proximal duodenum in presence of atropine (3 microM) and guanethidine (3 microM). EDA produced a concentration-(0.03-3 microM)-dependent relaxation which was potentiated when the preparations were exposed to GABA during the equilibration period. The GABA-induced potentiation of the response to EDA was prevented by nipecotic acid, an inhibitor of GABA uptake. The response to EDA was partially inhibited by 3-mercaptopropionic acid, a known inhibitor of GABA release. However, contrary to the relaxant response produced by exogenous GABA, the EDA-induced relaxation was picrotoxin-(0.1 microM)-resistant. In preparations pre-exposed to GABA, the response to EDA was partially tetrodotoxin-(1 microM)-sensitive. By contrast, in preparations not exposed to GABA, the EDA-induced relaxation was totally tetrodotoxin resistant. The response to EDA was abolished or largely inhibited in preparations excised from rats in which the proximal duodenum was chemically denervated by exposure (2 weeks before), to benzalkonium chloride (BZK). Likewise, the indirect relaxations produced by electrical field simulation. DMPP, capsaicin or GABA were abolished by BZK pretreatment while noradrenaline was still effective. These findings indicate that the relaxant response to EDA is neurogenic in origin, while being largely tetrodotoxin-resistant. A GABAergic mechanism could be involved but also other inhibitory transmitter(s) should be taken into account. EDA appears a useful tool to study the inhibitory non-adrenergic non-cholinergic innervation of the rat proximal duodenum.

3-Mercaptopropionic Acid↗
PubMed1989

Effect of ruthenium red on responses mediated by activation of capsaicin-sensitive nerves of the rat urinary bladder.

(1) Topical administration of Ruthenium Red (10-100 microM in saline) to the serosal surface of the urinary bladder in urethane-anesthetized rats prevented the motor response of the urinary bladder to topical administration of capsaicin and protected the sensory fibers from capsaicin desensitization, but had no effect on the volume-evoked contractions (micturition reflex). At 1 mM increased bladder capacity and decreased amplitude of micturition contraction were observed. (2) At 100 microM, topical Ruthenium Red prevented the blood pressure rise produced by topical administration of capsaicin onto the bladder but did not affect the blood pressure rise produced by sudden bladder distension in spinal rats. (3) After intrathecal administration, Ruthenium Red (80-800 ng/rat) produced a long lasting inhibition of the micturition reflex in urethane-anesthetized rats, this effect being evident in both vehicle- or capsaicin- (50 mg/kg s.c. 4 days before) pretreated rats. At 800 ng/rat, intrathecal Ruthenium Red did not affect the blood pressure rise produced by topical administration of capsaicin onto the rat bladder nor that produced by bladder distension. (4) These findings provide further evidence that Ruthenium Red acts quite selectively as a "capsaicin antagonist" preventing both reflex and "efferent" responses activated by peripherally administered capsaicin. By contrast, sensory impulse generation by a natural stimulus such as bladder distension is apparently unaffected by Ruthenium Red. The marked inhibition of the micturition reflex observed after intrathecal administration of Ruthenium Red does probably not involve an interaction with primary afferents in the spinal cord.

Administration, Topical↗
PubMed1989

Discovery of antidepressant activity by forced swimming test may depend on pre-exposure of rats to a stressful situation.

Antidepressant-induced anti-immobility effects have been assessed in animals exposed or not to a pretest session using the forced swimming test. Desipramine, maprotiline, mianserine (15 and 30 mg/kg), nomifensine (2.5 and 5 mg/kg), d-amphetamine (1 and 2 mg/kg) and muscimol (1 and 2 mg/kg), unlike imipramine (15 and 30 mg/kg), LY-171555 (0.1 and 0.2 mg/kg) and scopolamine (0.5 and 0.1 mg/kg), did not reduce immobility time in rats which had not received the pretest session. On the other hand, all of the drugs tested reduced immobility time in rats exposed to a pretest session. In addition, the degree of antiimmobility effects of desipramine (20 mg/kg) and nomifensine (5 mg/kg) increased proportionally with the level of water (0, 4, 15 and 30 cm) to which animals were exposed at the time of pretest. Furthermore, desipramine reduced immobility time in rats pre-exposed to types of stress different from forced swimming, cold, restraint or foot-shock. All drugs were injected intraperitoneally three times, 24, 5 and 1 h before testing. The present findings suggest that a stressful pretest session may reveal pharmacological properties of antidepressants in the forced swimming test. This is also substantiated by the fact that diazepam (2.5 and 5 mg/kg) administered 30 min before the swimming pretest antagonized the anti-immobility effect of 15 mg/kg desipramine.

Animals↗
PubMed1989

A model to measure anticipatory anxiety in mice?

Among animals from the same cage, mice removed last had a higher temperature compared to those removed first. This phenomenon a) persisted 2 and 24 h later; b) was present regardless of the number of the animals (5, 10, 15 and 20) in each cage, c) was independent of whether the number of animals was reduced or maintained constant in the cage and d) could even be observed by reversing the order of removal of the animals from the cage. In addition, the fewer the animals allocated to a cage the greater the percentage of those which became hyperthermic. This rise in rectal temperature of mice removed last was prevented by diazepam (2.5 and 5 mg/kg PO, 30 min), nitrazepam (2 and 4 mg/kg PO, 30 min) but not by imipramine (15 and 30 mg/kg PO, 60 min) or haloperidol (0.5 and 1 mg/kg PO, 60 min) and was observed in a greater percentage of mice following subcutaneous yohimbine treatment (2 mg/kg, 60 min). This phenomenon does not seem to depend on physical exercise due to an attempt to escape, since no correlation appears to exist between motor activity (open-field) and rise in rectal temperature. These data would seem to indicate that hyperthermia in the last animals may represent a new tool for studying the neurobiology of anticipatory(?) anxiety.

Animals↗
PubMed1989

Human isolated small intestine: motor responses of the longitudinal muscle to field stimulation and exogenous neuropeptides.

(1) Longitudinal muscle strips from the human small intestine (jejunum/ileum) responded to electrical field stimulation (1-50 Hz) with frequency-related primary contractions which were largely atropine- (3 microM) sensitive. When the tone was raised by addition of galanin (0.3-1 microM), prostaglandin (PG) E2 (1-10 microM) or neurokinin A (NKA, 0.1 microM), a frequency-related relaxation was evident which was potentiated by atropine. All the responses to field stimulation were abolished by tetrodotoxin (1 microM), thus indicating their neural origin. (2) The atropine-sensitive primary contraction to field stimulation was virtually abolished by omega conotoxin fraction GVIA (CTX, 0.1-0.3 microM) while the relaxations were CTX-resistant. The field stimulation-induced relaxations, which were observed in the presence of atropine and guanethidine (3 microM), were also unaffected by apamin (0.1 microM). (3) NKA and substance P (SP) produced a concentration- (1 nM-1 microM for both peptides) related contraction, NKA being about 53 times more potent than SP. [Pro9]SP sulphone and [MePhe7]-NKB, selective agonists of the NK-1 and NK-3 receptor, respectively, were barely effective. On the other hand, [beta Ala8]NKA(4-10), a selective NK-2 receptor agonist, had a potent contractile activity, similar to that of NKA. (4) Galanin (1 nM-1 microM) produced an atropine- and tetrodotoxin-resistant concentration-related contraction of longitudinal muscle of human isolated small intestine. The response to galanin did not show any sign of fading and was particularly suitable to study the evoked relaxations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Release of substance P- and calcitonin gene-related peptide-like immunoreactivity and motor response of the isolated guinea pig gallbladder to capsaicin.

The aim of this study was to assess whether a local motor response to capsaicin could be observed in the isolated guinea pig gallbladder and to discover the mechanism involved. Capsaicin produced a contraction of this organ that exhibited desensitization, suggesting a specific action on sensory nerves. In preparations preexposed to capsaicin to produce a functional blockade of the capsaicin-sensitive sensory fibers, the contractile response to field stimulation was unaffected as compared with controls. Tachykinins (substance P and neurokinin A) produced a concentration-related contraction of this organ, neurokinin A being more potent than substance P. Spantide, a tachykinin antagonist, markedly inhibited the capsaicin-induced gallbladder contraction, leaving the atropine-sensitive response to field stimulation unaffected. Calcitonin gene-related peptide (CGRP) produced a concentration-related relaxation, which was tetrodotoxin-resistant, suggesting a direct effect on muscle cells. Repeated administration of CGRP produced desensitization. At this stage, application of capsaicin produced a contractile response much larger than in controls. Both substance P- and CGRP-like immunoreactivity were detected in the guinea pig gallbladder by radioimmunoassay and were significantly reduced after systemic capsaicin desensitization. Capsaicin induced the simultaneous release of substance P- and CGRP-like immunoreactivity from superfused isolated gallbladders. These findings indicate that capsaicin-sensitive nerves in the guinea pig gallbladder can produce a local motor response involving the release of multiple neuropeptides. In the guinea pig gallbladder, tachykinins and CGRP might act as "physiologic antagonists," as observed in other viscera from rats and guinea pigs.

Animals↗
PubMed1989

Experimental procedure to favor an otherwise undetectable potential rat muricidal behavior.

We hypothesized that variation in mouse aggressiveness could, at least in part, affect muricidal attitude of rats, therefore we introduced a sedated (diazepam 50 mg/kg/PO) instead of a normal (nonsedated) mouse into a cage with a rat. Rats were challenged with sedated or nonsedated mice for two-four days. It was found that a) the percentage (40-60%) of rats which killed a sedated mouse was higher than that (about 10%) of those which killed a nonsedated mouse; b) rats trained to kill a sedated mouse did not kill a nonsedated mouse and c) rats which did not kill a nonsedated mouse did not kill a sedated mouse. The present results indicate that the first experience in the presence of a sedated mouse uncovers a muricidal behavior which persists upon exposure to subsequent similar experimental conditions. This behavior undergoes seasonal variations, reaching a maximum in September-October and a minimum in February-March.

Aggression↗
PubMed1989

Dermorphin inhibits micturition reflex in rats at a central site of action.

Intrathecal dermorphin (0.8-80 ng) or [D-Ala2, D-Leu5]-enkephalin (DADLE, 5.7-171 ng) produced a dose-related marked inhibition of reflex micturition in urethane-anesthetized rats until voiding was suppressed and overflow incontinence ensued. These effects of dermorphin or DADLE were promptly abolished by i.v. naloxone (0.2 mg/kg). The inhibitory effect of dermorphin but not that of DADLE was partially prevented by systemic capsaicin desensitization (50 mg/kg s.c., 4 days before). Intravenous dermorphin had little or no effect on micturition up to 8 micrograms/kg.

Animals↗
PubMed1989

Opioid-like action of eseroline on micturition reflex in rats.

1. Eseroline (3-10 mg/kg s.c.), the first product of metabolic breakdown of eserine (physostigmine) markedly increased bladder capacity and decreased voiding efficiency of reflex micturition in rats. 2. Eserine had an opposite effect on bladder function in vivo, while morphine (1-3 mg/kg s.c.) reproduced the action of eseroline. The effects of eseroline or morphine were prevented by naloxone which per se reduced bladder capacity. 3. In vitro both eserine and eseroline potentiated the cholinergic component of the twitch response to field stimulation of the rat bladder and this effect was atropine-sensitive while morphine had no effect. 4. These findings provide further support to the notion that eseroline possesses both eserine- and opioid-like actions, but this latter predominates in determining its actions on bladder function in vivo.

Acetylcholine↗