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A Meli

Publications and source records attributed to A Meli.

At least 73 records · Page 4Linked to original sources
PubMed1989

Further studies on the motor response of the human isolated urinary bladder to tachykinins, capsaicin and electrical field stimulation.

1. Muscle strips from the dome of the human urinary bladder responded to field stimulation with contractions which were atropine- (3 microM) and tetrodotoxin- (1 microM) sensitive. These contractions were sensitive to omega conotoxin (CTX, 0.1 microM). The atropine- and tetrodotoxin-resistant contractions produced by field stimulation were totally unaffected by CTX. 2. DMPP (30-100 microM), a nicotinic agonist, produced transient bladder contractions which were hexamethonium- and atropine-sensitive. 3. Tachykinins produced a contraction of the human bladder. Among several synthetic tachykinin analogs only those having activity at the NK-2 receptor produced a consistent contractile response. 4. Either capsaicin (1 microM) or calcitonin gene-related peptide (10 nM-0.1 microM) had no motor effect. At 10 microM, capsaicin exerted a depressant effect on nerve-mediated contractions but this effect did not exhibit desensitization. 5. These findings provide evidence that NK-2 receptors are the main if not the sole mediators of the contractile response of the muscle from the dome of the human isolated bladder to tachykinins. 6. No evidence was found for a tachykininergic component in the excitatory response to field stimulation nor for motor responses mediated by capsaicin-sensitive nerves. 7. CTX-sensitive calcium channels are probably present on cholinergic nerve terminals in the human bladder muscle.

Adult↗
PubMed1989

The effect of calcium free medium and nifedipine on the release of substance P-like immunoreactivity and contractions induced by capsaicin in the isolated guinea-pig and rat bladder.

1. Capsaicin produced a prompt release of substance P-like immunoreactivity (SP-LI) from superfused mucosa-free muscle strips excised from the guinea-pig urinary bladder. A second application of capsaicin had no further effect, indicating desensitization. 2. Neither tetrodotoxin (1 microM) or nifedipine (10 microM) had any inhibitory effect on SP-LI release by capsaicin nor influenced the establishment of the desensitized state. Nifedipine produced per se some SP-LI release. 3. SP-LI release by capsaicin was abolished by incubation in a Calcium(Ca)-free medium containing EDTA (1.0 mM) which also afforded a partial protection toward desensitization. A lower EDTA concentration (0.1 mM) did not suppress SP-LI release by capsaicin but still inhibited desensitization. 4. When the concentration of CaCl2 in the medium was lowered to 1/10-1/100 of that present in normal Krebs solution, capsaicin still evoked a marked SP-LI release and desensitization occurred. In a nominally Ca free medium (maximal Ca concentration due to impurities was 6.7 microM) SP-LI release was still observed and desensitization was incomplete. 5. In a nominally Ca free medium, removal of Mg ions enhanced the SP-LI release induced by capsaicin and enhanced desensitization. 6. In functional studies, nifedipine greatly reduced or abolished the capsaicin- or SP-induced contraction of the rat or guinea-pig isolated bladder but did not prevent desensitization. Likewise, SP-LI depletion in the rat bladder following systemic capsaicin desensitization was not prevented by nifedipine pretreatment. On the other hand, the protective action of Ca free media (containing EDTA) was confirmed in organ bath studies (guinea-pig bladder). 7. These findings indicate that: (a) the requirements of extracellular calcium for activation of neuropeptide release from sensory nerves by capsaicin are very low; (b) both excitation of sensory fibers (SP-LI release) and desensitization are dependent upon the presence of extracellular calcium and (c) L-type voltage-sensitive Ca channels are not likely to be involved in the actions of capsaicin on sensory nerve terminals.

Animals↗
PubMed1989

Infravesical outflow obstruction in rats: a comparison of two models.

1. A new model of infravesical outflow obstruction was developed in male rats by the repeated s.c. administration of testosterone for 5-15 days (3 mg/kg die). The effects of this treatment which produced a 65% increase of prostate weight (10 days) on bladder voiding was evaluated in urethane anesthetized rats by the transvesical infusion of saline and compared to the cystometric alterations produced by application of a silk ligature at urethral level in female rats (4-8 weeks before) as described by Malmgren et al. (1987a, b). 2. Testosterone-pretreatment for 10 days produced little changes in bladder weight, bladder capacity or amplitude of micturition contraction but determined a marked increase in residual volume, indicating that infravesical outflow obstruction impaired significantly bladder voiding. Furthermore, detrusor instability was observed in the majority of testosterone-treated rats. 3. The participation of an active component to voiding impairment in testosterone-treated rats was suggested by the effect of intravenous prazosin which improved voiding efficiency. 4. In urethra-ligated female rats there was a marked increase in bladder weight which was paralleled by a dramatic alteration in micturition reflex that is marked increase in bladder capacity and residual volume. 5. It is concluded that these two models of infravesical outflow obstruction produce cystometric patterns simulating the urodynamic alterations observed in patients with benign prostatic hyperplasia and are potentially suitable for development of drugs in this field.

Animals↗
PubMed1989

Further studies on mechanisms regulating the voiding cycle of the rat urinary bladder.

1. The effect of transection of pudendal or hypogastric nerves and of various pharmacological pretreatments on the bladder voiding cycle elicited by saline filling was investigated in urethane-anesthetized rats. 2. Sectioning of pudendal nerves reduced efficiency of the expulsive phase of the voiding cycle while sectioning of hypogastric nerves enhanced voiding efficiency and reduced residual volume. 3. An increased voiding efficiency was also observed in 6-hydroxydopamine-treated rats. 4. Atropine and physostigmine decreased and increased voiding efficiency, respectively. Indomethacin pretreatment produced a marked increase in residual volume. 5. These findings indicate that the autonomic innervation of the bladder and urethra as well as production of local factors such as prostanoids regulates not only the collecting phase of the cystometragram but also influence markedly voiding efficiency.

Animals↗
PubMed1989

Topical versus systemic capsaicin desensitization: specific and unspecific effects as indicated by modification or reflex micturition in rats.

The aim of this study was to determine the acute and delayed effect of topical application of high concentrations of capsaicin on the rat urinary bladder on micturition reflex and compare the effects of "topical" bladder desensitization with those produced by systemic (subcutaneous administration) capsaicin desensitization. On acute application, capsaicin (1-3%) produced a transient bladder contraction, not observed in capsaicin-pretreated rats. After a transient increase in excitability of the micturition reflex, topical capsaicin suppressed micturition and overflow incontinence ensued which was reverted by intravenous injection of 4-aminopyridine. Topical capsaicin also abolished reflex micturition in rats which had been systemically treated with capsaicin as adults (50 mg/kg, 7 days before) and reduced significantly the neurogenic bladder contractions produced by intravenous dimethylphenylpiperazinium or neurokinin A, while the direct (myogenic) response to neurokinin A was unaffected. In rats whose bladder was pre-exposed to 1-3% topical capsaicin (7 days before) the micturition reflex was affected in a manner which is qualitatively and quantitatively similar to that observed in rats treated with capsaicin as adults, e.g. increase in bladder capacity with no change in voiding efficiency. Topical capsaicin desensitization of the rat urinary bladder was shown to produce a selective impairment of bladder sensory nerves without any sign of desensitization in other areas of the body using both functional (hot plate, wiping, plasma extravasation) and neurochemical (determination of substance P-like immunoreactivity) assays. Systemically administered capsaicin (7 days before) had little effect on reflex micturition at 12.5 mg/kg but the change in bladder capacity produced at a dose of 25 mg/kg was comparable with that produced at 350 mg/kg. These findings provide evidence that selective desensitization of peripheral terminals of capsaicin-sensitive nerves of the rat urinary bladder inactivates their sensory and "efferent" function in a manner similar to that observed after systemic capsaicin desensitization in adult rats. The functional deficit of reflex micturition produced in this way can be overcome by increasing the stimulus to void. By contrast, neonatal capsaicin desensitization produced a long lasting abolition of reflex micturition. These data are in keeping with the hypothesis that adult versus neonatal capsaicin desensitization may be used as a tool to distinguish between two sets of sensory nerves in the rat urinary bladder.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗
PubMed1989

Cystometric evidence that capsaicin-sensitive nerves modulate the afferent branch of micturition reflex in humans.

Intravesical instillation of capsaicin (0.1 to 10 microM) in six patients (five with hypersensitive disorders of the lower urinary tract, one with benign prostatic hyperplasia) produced a concentration-related reduction of the first desire to void, bladder capacity and pressure threshold for micturition. At a threshold concentration of one microM, capsaicin also produced a warm to burning sensation referred to the suprapubic area during the collecting phase and to the urethra during micturition. All the patients with hypersensitive disorders of the lower urinary tract reported disappearance or marked attenuation of their symptoms for a few days after capsaicin application. In three other patients with hypersensitive disorders of the lower urinary tract, intravesical instillation of capsaicin's vehicle (0.1% ethanol in saline) did not produce significant cystometric changes nor modify the symptomatology. These observations provide the first indication that capsaicin-sensitive structures (nerves?) may be present in the human urinary bladder as they have been shown to occur in various other species.

Administration, Intravesical↗
PubMed1989

A method for studying pain arising from the urinary bladder in conscious, freely-moving rats.

A new technique has been developed suitable for quantitative studies on physio-pharmacology of pain arising from the urinary bladder in conscious freely-moving rats. The method involves the intravesical instillation of xylene or its vehicle (0.3 cc of silicone oil) through a catheter chronically implanted into the rat bladder. The instillation of xylene (10 to 100%) produced behavioural effects (licking of lower abdomen or perineal region, hind paws hyperextension) suggestive of visceral pain. All the behavioural responses produced by xylene instillation were prevented by extrinsic bladder denervation (pelvic ganglionectomy). Morphine HCl (two to five mg./kg. s.c., 30 min. before) or (+/-)-baclofen (2.5-10 mg./kg. s.c., 60 min. before) reduced or abolished the response to xylene instillation, thus indicating that the action of analgesic drugs can be quantitated using the present model.

Animals↗
PubMed1989

Functional studies on the cholinergic and sympathetic innervation of the rat proximal urethra: effect of pelvic ganglionectomy or experimental diabetes.

1. Isolated rings of rat proximal urethra contracted in response to acetylcholine, noradrenaline, phenylephrine, tachykinins or field stimulation. In the presence of field stimulation-induced contractions, isoprenaline or CGRP produced an inhibitory effect on evoked contractions. 2. Electrical field stimulation produced frequency-related contractions which, when using trains of stimuli, consisted of a phasic and a tonic response. These contractions were abolished by tetrodotoxin (1 microM) but unaffected by hexamethonium (10 microM). 3. Atropine (3 microM) produced a partial inhibition of these nerve-mediated contractions, slightly more evident on the tonic than the phasic response. In the presence of atropine (3 microM), phentolamine (3 microM) or prazosin (1-10 nM) produced an almost complete inhibition of the response to field stimulation. 4. After bilateral removal of the pelvic ganglia, electrical field stimulation was still able to induce tetrodotoxin-sensitive contractions of the rat proximal urethra. However, the inhibitory effect of atropine was much reduced as compared to controls, while the phentolamine-sensitive portion of the response was increased. 5. DMPP (0.1 mM) a nicotinic receptor agonist, produced a contraction (phasic and tonic components) which was strongly inhibited by hexamethonium (10 microM), abolished by prazosin (1 microM) and reduced by tetrodotoxin (3 microM). 6. In urethral rings from diabetic rats (i.v. streptozotocin 7-9 weeks before) the contractile response to acetylcholine or noradrenaline as well as the response to field stimulation were unchanged as compared to controls. 7. Capsaicin (1 microM) produced an inhibitory effect on the nerve-mediated contractions of the rat proximal urethra. This response was abolished by pelvic ganglionectomy but was unaffected in streptozotocin-treated rats. 8. These findings provide functional evidence that both cholinergic and noradrenergic nerves mediate the contractions of the rat proximal urethra. In addition, capsaicin-sensitive sensory nerves can produce certain local motor responses through release of endogenous neuropeptides. In vivo studies are needed to examine the interplay between these differents sets of motor nerves in the regulation of proximal urethra motility.

Acetylcholine↗
PubMed1989

Effects of tachykinins and selective tachykinin receptor agonists on vascular permeability in the rat lower urinary tract: evidence for the involvement of NK-1 receptors.

1. Intravenous administration of three mammalian tachykinins (substance P, neurokinin A and neurokinin B) and three non-mammalian tachykinins (physalaemin, eledoisin and kassinin) induced dose-dependent increases in vascular permeability, as measured by Evans blue leakage technique, in various segments of the lower urinary tract (bladder dome and neck, proximal urethra, ureters) in urethane-anaesthetized rats. 2. Plasma extravasation induced by substance P (3.71 nmol kg-1 i.v.) was unaffected by pretreatment with antihistaminic drugs or methysergide. 3. A comparison of the relative potencies of various tachykinins did not allow characterization of a distinct type of receptor involved in the increase in vascular permeability. 4. The effects of tachykinin-related peptides which are selective agonists at the NK-1 (substance P-methylester, [Pro9]-SP-sulphone), NK-2 receptor [( Nle10]-NKA(4-10] or NK-3 receptor [( MePhe7]-NKB(4-10) and Senktide) indicated that NK-1 agonists are effective in the whole lower urinary tract, while NK-2 or NK-3 agonists are inactive or weakly active. 5. [beta-Ala4, Sar9]-SP(4-11)-sulphone, a selective NK-1 receptor agonist devoid of histamine-releasing properties, was highly potent and effective in producing plasma extravasation in the rat lower urinary tract. 6. These findings indicate that NK-1 receptors mediate the effect of intravenous tachykinins on vascular permeability in the rat lower urinary tract, through a histamine-independent mechanism.

Animals↗
PubMed1989

Potent contractile activity of endothelin on the human isolated urinary bladder.

Endothelin (1 nM-0.3 microM) produced a concentration-related contraction of mucosa-free muscle strips excised from the dome of the human urinary bladder. The response to endothelin was unaffected by either atropine (1 microM) or nifedipine (1 microM) at concentrations that abolished the response to carbachol and KCl, respectively. These findings indicate that mechanisms other than activation of dihydropyridine- and voltage-sensitive calcium channels may be involved in the action of endothelin on smooth muscles.

Adult↗
PubMed1989

GABAA receptor-mediated positive inotropism in guinea-pig isolated left atria: evidence for the involvement of capsaicin-sensitive nerves.

1. Isolated left atria from reserpine-pretreated guinea-pigs, electrically driven (3 Hz) in the presence of atropine (1 microM), phentolamine (0.3 microM) and propranolol (1 microM), responded to a train of stimuli (10 Hz for 2.5s) with a delayed neurogenic positive inotropic response which was insensitive to hexamethonium (10 microM) but abolished by either tetrodotoxin (1 microM), omega-conotoxin (0.1 microM), in vitro capsaicin desensitization or desensitization to calcitonin gene-related peptide (CGRP). 2. In these experimental conditions, gamma-aminobutyric acid (GABA) produced a concentration-related (10 microM-1 mM) positive inotropic response similar to that produced by electrical field stimulation. The effect of GABA was competitively antagonized by bicuculline methiodide (10 microM), a GABAA receptor antagonist. 3. The selective GABAA receptor agonists, muscimol and homotaurine mimicked the positive inotropic effect of GABA while baclofen, the selective GABAB receptor agonist, did not. 4. The action of GABA (1 mM) was abolished by either tetrodotoxin (1 microM), omega-conotoxin (0.1 microM), in vitro capsaicin desensitization or desensitization to CGRP, while it was unaffected by hexamethonium. In contrast, the inotropic response to CGRP was unaffected by tetrodotoxin, omega-conotoxin, bicuculline methiodide, hexamethonium or in vitro capsaicin desensitization, but was abolished by CGRP desensitization. 5. In the spontaneously beating guinea-pig right atrium, GABA (1 microM) produced a small and transient positive chronotropic effect that was no longer observed after in vitro desensitization with capsaicin (1 microM). 6. In the guinea-pig isolated perfused heart from reserpine-pretreated animals (with atropine, phentolamine and propranolol in the perfusion medium), GABA (1 microM) produced a transient tachycardia and a small increase in coronary flow. Both capsaicin (1 microM) and CGRP (1 microM) produced marked tachycardias and increases in coronary flow. After exposure to capsaicin (1 microM), no effect of GABA could be detected. 7. We conclude that, in the guinea-pig heart, GABAA receptors, presumably located on the preterminal region of capsaicin-sensitive sensory nerves, initiate a conducted impulse (since it is tetrodotoxin-sensitive) which leads to transmitter release (endogenous CGRP-like material) by activation of omega-conotoxin-sensitive, voltage-sensitive calcium channels and a functional response.

Animals↗
PubMed1989

Prejunctional modulatory action of neuropeptide Y on peripheral terminals of capsaicin-sensitive sensory nerves.

1. We have determined the effect of neuropeptide Y (NPY) on motor responses produced by activation of capsaicin-sensitive primary afferents in the guinea-pig isolated left atria (reserpine-pretreatment, atropine in the bath) and bronchi (atropine and indomethacin in the bath) using capsaicin itself and electrical field stimulation as stimuli. 2. In both preparations, NPY inhibited or suppressed the response produced by electrical field stimulation while leaving the response to a submaximal concentration of capsaicin unaffected. 3. NPY had no effect on motor responses produced by a submaximal concentration of calcitonin gene-related peptide (atria) or neurokinin A (bronchi), the putative endogenous mediators of the responses produced by activation of the 'efferent' function of sensory fibres in these preparations. 4. We conclude that NPY exerts a prejunctional inhibitory action on transmitter release from peripheral endings of capsaicin-sensitive nerves. Failure of NPY to modulate responses activated by capsaicin provides further evidence for the existence of two independent modes of activation of the 'efferent' function of capsaicin-sensitive sensory nerves.

Animals↗
PubMed1989

Multiple mechanisms in the motor responses of the guinea-pig isolated urinary bladder to bradykinin.

1. Bradykinin (1 nm-1 microM) produced a contraction of bladder strips excised from the dome of the guinea-pig urinary bladder, an effect which was greatly enhanced by removal of the mucosal layer or by thiorphan (10 microM). All subsequent experiments were performed in mucosa-free strips and in the presence of thiorphan. 2. In carbachol (5 microM)-contracted strips, bradykinin produced a concentration (1 nm-1 microM)-dependent transient relaxation. 3. Kallidin was slightly more potent than bradykinin in producing a contraction and a relaxation of the carbachol-induced tone. By contrast, [des-Arg9]-bradykinin, a selective B1 receptor agonist was barely effective up to 1 microM. 4. The contractile response to bradykinin was: (a) unaffected by either tetrodotoxin (1 microM), in vitro capsaicin desensitization (10 microM for 30 min) or apamin (0.1 microM); (b) antagonized by indomethacin (5 microM), the prostaglandin receptor antagonist SC-19220 (100 microM) or the B2 receptor antagonist [D-Arg0, Hyp3, Thi5,8, Phe7]-bradykinin (10 micron) and (c) almost abolished by nifedipine (1 microM). 5. The antagonism of the contractile response to bradykinin produced by indomethacin and SC-19220 was non-additive while that produced by indomethacin and the B2 receptor antagonist was additive. 6. The relaxant response to bradykinin was unaffected by tetrodotoxin, in vitro capsaicin desensitization or indomethacin but antagonized in a competitive manner by the B2 receptor antagonist. Further, this response was abolished by apamin (0.1 microM) but unaffected by glibenclamide (1 microM). 7. Bradykinin (10 microM) produced a consistent release of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) but not substance P-LI from the guinea-pig bladder muscle. CGRP-LI release by bradykinin was greatly reduced in bladders exposed to indomethacin. [des-Arg9]-bradykinin (10 microM) was ineffective. 8. We conclude that: (a) bradykinin-induced contraction involves activation of both B2 receptors and prostanoid synthesis, via distinct mechanisms which act by inducing calcium influx via nifedipine-sensitive channels; (b) bradykinin-induced relaxation involves activation of B2 receptors and opening of apamin-sensitive potassium channels; (c) bradykinin stimulates sensory nerves in this tissue largely via prostanoid production.

Animals↗
PubMed1989

Multiple sources of calcium for contraction of the human urinary bladder muscle.

1. KCl, carbachol, neurokinin A and endothelin produced concentration-dependent contractions of mucosa-free muscle strips from the dome of the human urinary bladder. The maximal response to carbachol or neurokinin A exceeded that to KCl, while the maximal response to endothelin approached that to KCl. 2. Nifedipine (1 microM) abolished the response to KCl, reduced the response to carbachol or neurokinin A but had no effect on the response to endothelin. Bay K 8644 (1 microM) markedly potentiated the response to KCl but had little or no effect on the response produced by the other stimulants. 3. Superfusion of the strips with a nominally calcium (Ca)-free medium containing EDTA (1 mM) for 30 min markedly reduced the response to carbachol, neurokinin A and endothelin, although a small response was still evident at high concentrations. Likewise, after a prolonged (60 min) superfusion of the strips with a high K (80 mM) Ca-free medium plus EDTA (1 mM) these three agonists still produced a small contractile response. 4. The nifedipine (1 microM) resistant response to carbachol, neurokinin A or endothelin was markedly depressed by LaCl3 (1 mM). In contrast, the nifedipine-(1 microM) resistant response to carbachol was not modified by NiCl2 (0.1 mM) or omega-conotoxin (0.1 microM). 5. Caffeine produced divergent effects depending upon the temperature of incubation: a relaxation at 37 degrees C and a concentration-dependent (2.5-20 mM) contraction at 25 degrees C. The latter was markedly inhibited by procaine (3 mM) but unaffected by nifedipine (1 microM). 6. After a prolonged (60 min) superfusion with a high K, Ca-free medium containing EDTA the response to carbachol (100 microM) was abolished by previous exposure to procaine (3 mM). Conversely, the response to endothelin (1 microM) was unaffected by procaine. The response to endothelin in these experimental conditions was also resistant to LaCl3 (1 mM). 7. These findings indicate that multiple sources of Ca are mobilized for contraction of the human bladder muscle by different stimulants. Dihydropyridine- and voltage-sensitive Ca channels provide the major if not the sole source of Ca for the response to KCl, play some role in the response to muscarinic (carbachol) or NK-2 tachykinin receptor stimulation but are not involved in the response to endothelin. Carbachol, neurokinin A and endothelin all mobilize a Ca pool (either extracellular or located at membrane level) which is LaCl3-sensitive but nifedipine-resistant. Neither T- nor N-type channels appear to be involved in the response to carbachol. In addition, these agents mobilize a tightly bound Ca pool independently from membrane depolarization. This latter pool is probably a procaine-sensitive intracellular source of activator Ca mobilized by caffeine and carbachol. The failure of procaine to prevent the response to endothelin in high K, Ca-free medium raises the possibility that this peptide mobilizes an intracellular source of activator Ca, distinct from the caffeine- and carbachol-sensitive pool.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Increase in gastric secretion induced by 2-deoxy-D-glucose is impaired in capsaicin pretreated rats.

Gastric acid secretion was determined following intravenous administration of 2-deoxy-D-glucose (2-DG; 60 mg kg-1) or electrical stimulation of the vagus nerve in urethane-anaesthetized rats pretreated when newborn with either capsaicin or the vehicle. The secretory response to 2-DG was substantially reduced in the capsaicin pretreated rats, while that induced by electrical vagal stimulation (1 mA, 1 ms. 3 Hz) was unaffected. These results suggest that capsaicin-sensitive fibres are involved in the afferent branch of the reflex response activated by 2-DG to stimulate gastric acid secretion.

Animals↗
PubMed1989

Effect of acute or chronic administration of imipramine on spinal and supraspinal micturition reflexes in rats.

Acute imipramine administration (15 mg/kg i.p. 60 min before) increased the threshold for activating the spinal but not the supraspinal vesico-vesical micturition reflex in urethane-anesthetized rats. On the other hand, "chronic" imipramine administration (15 mg/kg i.p./day for 5 consecutive days) increased selectively the threshold of the supraspinal micturition reflex. Intravenous administration of cumulative doses of imipramine (up to 14 mg/kg) exerted a progressive inhibitory effect on the supraspinal reflex and voiding efficiency, possibly related to direct inhibition of muscular contractility at the bladder level. However, with the dose regimen used to compare the action of imipramine on spinal and supraspinal reflexes (15 mg/kg i.p., 60 min before), imipramine did not affect the volume-pressure curve or myogenic activity in decentralized bladders (bilateral removal of pelvic ganglia). The effect of acute imipramine on threshold of the spinal vesico-vesical reflex was absent in rats receiving oral p-chlorophenylalanine to deplete 5-hydroxytryptamine stores in the central nervous system. On the other hand, p-chlorophenylalanine pretreatment did not prevent the action of chronic imipramine administration on the supraspinal reflex. Acute administration of desipramine, the major metabolite of imipramine, increased threshold of the spinal but not supraspinal micturition reflex. These findings indicate that the ability of imipramine to modulate vesico-urethral motility at the central nervous system level may involve different mechanisms. Inhibition of 5-hydroxytryptamine reuptake in nerve terminals may be important for the acute modulatory effect of imipramine on the spinal reflex.

Animals↗
PubMed1989

Effect of thiorphan on tachykinin-induced potentiation of nerve-mediated contractions of the rat isolated vas deferens.

We have assessed the ability of thiorphan, an inhibitor of enkephalinase, to influence the potentiation of the nerve-mediated contractions of the rat isolated vas deferens (pars prostatica) by mammalian tachykinins [substance P, (SP); neurokinin A (NKA); and neurokinin B (NKB)] and selective tachykinin agonists. In the absence of thiorphan, the rank order of potency of mammalian tachykinins was NKA greater than NKB much greater than SP. The maximal response to SP did not exceed 40% of that to NKA or NKB. Thiorphan (10 microM) had no effect on twitches per se, but increased the potency and maximum effect of mammalian tachykinins. [Pro9]-SP sulfone, a selective NK-1 receptor agonist had no effect, either in the absence or presence of thiorphan. [MePhe7]-NKB had some potentiating effect, but only at micromolar concentrations. [Nle10]-NKA (4-10) and [beta-Ala8]-NKA (4-10), two selective NK-2 agonists displayed good activity. [Nle10]-NKA (4-10) was potentiated by thiorphan. On the other hand, the action of [beta Ala8]-NKA (4-10) was completely thiorphan-resistant. These findings indicate that estimate of activity of tachykinins and tachykinin related peptides in this bioassay is influenced markedly by peptide degradation via a thiorphan-sensitive mechanism. NK-2 receptors are the main if not the sole mediators of the response to tachykinins in this bioassay organ.

Animals↗