[Effect of gamma-aminobutyric acid on cardiac inotropism in the anesthetized guinea pig].
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Adrenalectomy↗
Biomedical subjects
A Meli
Publications and source records attributed to A Meli.
Somatovesical and vesicovesical excitatory reflexes in urethane-anaesthetized rats.
The effect of spinal cord transection on excitatory somato- and vesicovesical micturition reflexes have been investigated in urethane-anaesthetized rats. In adult rats, 3 distinct types of excitatory reflexes to the bladder may be observed: a somatovesical reflex organized at spinal level and two vesicovesical reflexes organized at spinal and supraspinal level, respectively. In agreement with results of lesion experiments (Neurosci. Lett., 8 (1978) 27-33), bladder voiding is abolished following spinal cord transection although both somato- and vesicovesical reflexes may be demonstrated in acute spinal rats. Occurrence of the spinal vesicovesical reflex during the collecting phase of the cystometrogram appears to be inhibited by a supraspinal inhibitory pathway.
Anesthesia↗
The motor effect of the capsaicin-sensitive inhibitory innervation of the rat ureter.
Neurokinins activate a series of tetrodotoxin (TTX)-insensitive rhythmic contractions of the rat isolated ureter. Field stimulation or capsaicin (1-3 microM) produced a transient inhibition of neurokinin-activated ureteral motility in preparations from control but not from capsaicin-pretreated (50 mg/kg s.c.) rats. The inhibitory action of field stimulation but not that of capsaicin was prevented by TTX. It is concluded that a capsaicin-sensitive inhibitory innervation exists in the rat ureter.
Animals↗
Suitability of urethane anesthesia for physiopharmacological investigations. Part 3: Other systems and conclusions.
The suitability of urethane anesthesia for physiopharmacological experiments in various systems is briefly reviewed. Urethane anesthesia appears to be suitable for various types of studies on respiratory function and on reflex activation of motility of the urinary bladder and some sections of the intestinal tract. However, urethane produces a variety of potentially disturbing side-effects at endocrine and renal level.
Adrenal Glands↗
Pharmacological evidence that at least two different non-adrenergic non-cholinergic inhibitory systems are present in the rat small intestine.
The nature of the non-adrenergic non-cholinergic (NANC) relaxation was studied in the proximal (duodenum) and distal (ileum) regions of the rat small intestine. In rat duodenum ATP (1 microM-1 mM) produced a concentration-dependent transient relaxation. In ileal segments it produced a slight inhibitory effect at low concentrations (1-10 microM) and a powerful concentration-dependent contractile effect at concentrations equal to or higher than 100 microM. Relaxation similar to that elicited by ATP can be induced in rat duodenum with the nicotinic stimulant dimethylphenylpiperazinium (DMPP, 0.1 mM) and with gamma-aminobutyric acid (GABA, 1 mM). DMPP had a similar inhibitory effect on distal ileum while GABA barely affected spontaneous activity in this preparation. TTX (0.5 microM)-sensitive relaxation can be elicited in both duodenal and ileal tissues by field stimulation at 0.1 Hz. In the rat duodenum this nerve-mediated relaxation was sensitive to ATP desensitization, nucleotide pyrophosphatase (0.25 U/ml) but resistant to the proteolytic enzyme alpha-chymotrypsin (2 U/ml). On the other hand the field stimulation (0.1 Hz)-induced relaxation in the distal ileum was unaffected by ATP desensitization (by using both low or high concentration of ATP) and by incubation of the preparation with the two enzymes. These findings provide pharmacological evidence that low frequency field stimulation activates at least two different inhibitory NANC systems in the rat small intestine. Adenosine-5'-triphosphate (ATP) appears to be involved as a major transmitter in the duodenal but not in the ileal NANC inhibitory mechanism(s).
Adenosine Triphosphate↗
Suitability of urethane anesthesia for physiopharmacological investigations in various systems. Part 2: Cardiovascular system.
Urethane produces a level of surgical anesthesia characterized by preservation of a number of cardiovascular reflexes. When the proper route of administration is used, and the use of unnecessarily high doses is avoided, urethane anesthesia appears to be suitable for a number of investigations at cardiovascular level. However in certain types of studies involving pharmacological stimulation of peripheral adrenoceptors urethane affects markedly the magnitude of the response under study.
Anesthesia↗
Effect of GABAergic drugs in the behavioral 'despair' test in rats.
Aminooxyacetic acid (AOAA, 25 mg/kg i.p.), muscimol (2 mg/kg i.p.) and 4,5,6,7-tetrahydroisooxazol-[4,5-c]-pyridin-3-ol (THIP, 5 and 10 mg/kg s.c.), but not baclofen (10 mg/kg i.p.) administered three times (24, 5 and 1 h before the test) decreased the immobility time of rats in the behavioral 'despair' test. At these doses, AOAA, muscimol and THIP reduced motor activity. Muscimol (2 mg/kg) and THIP (5 and 10 mg/kg) exerted the antiimmobility effect even after single dosing 1 h before the test. Picrotoxin (1 and 2 mg/kg i.p.), but not bicuculline (2 mg/kg i.p.), prevented the effect of both muscimol and THIP in the behavioral 'despair' test.
Acetates↗
Suitability of urethane anesthesia for physiopharmacological investigations in various systems. Part 1: General considerations.
The suitability of urethane anesthesia for physiopharmacological investigations is reviewed. Total dose administered and route of administration are recognized as factors having a great influence on both resting parameters and biological responses to drugs. A peculiar characteristic of urethane is represented by its ability to induce a surgical plane of anesthesia without affecting neurotransmission in various subcortical areas and the peripheral nervous system. This makes urethane a suitable general anesthetic for studying neural function in both central and peripheral nervous systems and accounts for the preservation of a number of reflex responses in urethane-anesthetized animals.
Acetylcholine↗
Capsaicin activates neurogenic non-adrenergic non-cholinergic relaxations of the isolated rat duodenum.
Capsaicin induces a transient relaxation of the isolated rat duodenum in the presence of atropine plus guanethidine. The relaxant effect of capsaicin was not observed in vitro in the duodenum of capsaicin-pretreated animals. Capsaicin-induced relaxation was antagonized by tetrodotoxin or cold storage (24 h at 4 degrees C). It is concluded that capsaicin produces a neurogenic relaxation of the rat duodenum by activating an intramural non-adrenergic non-cholinergic mechanism which inhibits intestinal motility.
Animals↗
The role of the capsaicin-sensitive innervation of the rat urinary bladder in the activation of micturition reflex.
Capsaicin applied on the serosal surface of the urinary bladder in urethane-anaesthetized rats produces two distinct types of motor effects: a tetrodotoxin-, hexamethonium- and lidocaine-insensitive 'tonic' contraction and a series of tetrodotoxin-, hexamethonium- and lidocaine-sensitive rhythmic contractions. Both 'tonic' and rhythmic contractions are abolished by bladder denervation indicating their neurogenic origin. The rhythmic but not the 'tonic' component of the contractile effect of capsaicin is abolished by spinal cord transection indicating activation of a supraspinal micturition reflex. The motor effects of topical capsaicin are unaffected by pretreatment with indomethacin or diphenhydramine plus cimetidine. Pretreatment with a large dose of subcutaneous (SC) capsaicin increases both volume and pressure threshold for micturition while amplitude of micturition contraction is unaffected. Moreover the spinal somatovesical reflex elicited by pinching of the perineal skin is unaffected by capsaicin-desensitization. The intracerebroventricular (ICV) administration of capsaicin reproduces the effects of SC capsaicin on the bladder response to saline filling. Rats pretreated with ICV capsaicin are as sensitive as controls in reacting to noxious heat (hot plate test) while the wiping response to instillation of capsaicin into one eye was abolished. These findings provide functional evidence for the presence in the rat urinary bladder of a capsaicin-sensitive innervation which subserves a sensory function in relaying volume/pressure information from detrusor muscle to central nervous system. Information carried through these capsaicin-sensitive fibers appears to be relevant for initiation of a supraspinal vesico-vesical micturition reflex. Functional evidence indicates that these fibers may terminate at supraspinal level.
Acetylcholine↗
Extrinsic origin of the capsaicin-sensitive innervation of rat duodenum: possible involvement of calcitonin gene-related peptide (CGRP) in the capsaicin-induced activation of intramural non-adrenergic non-cholinergic neurons.
Capsaicin produces a concentration-related relaxation of the longitudinal muscle of the rat isolated duodenum in the presence of atropine (3 microM) plus guanethidine (3 microM). This effect of capsaicin is partly (about 40%) antagonized by tetrodotoxin (1.0 microM) suggesting the involvement of intramural non-adrenergic non-cholinergic (NANC) neurons. The capsaicin-induced relaxations are unaffected by previous bilateral vagotomy or removal of the inferior mesenteric ganglion but are completely prevented by removal of the coeliac ganglia plus the superior mesenteric ganglion (72 h before). Acute duodenal denervation did not modify the response to capsaicin. Unlike various neuropeptides (substance P, kassinin, neurokinin A, cholecystokinin octapeptide, somatostatin, vasoactive intestinal polypeptide) only the calcitonin gene-related peptide (CGRP) closely mimicked, both qualitatively and quantitatively, the capsaicin-induced relaxations. The CGRP-induced relaxations were unaffected by hexamethonium and partly reduced (about 40%) by tetrodotoxin. In preparations desensitized to adenosine-triphosphate (ATP) a putative NANC inhibitory neurotransmitter of the rat duodenum, the effects of CGRP were reduced (about 30%) as compared to controls. After ATP-desensitization tetrodotoxin did not produce any further reduction of the CGRP-induced relaxations suggesting the involvement of endogenous ATP in the neuronal (tetrodotoxin-sensitive) component of the CGRP-induced relaxations. Either ATP- or CGRP-desensitization reduced (about 50 and 65% respectively) the amplitude of the capsaicin-induced relaxations.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Triphosphate↗
Does the behavioral "despair" test measure "despair"?
The behavioral "despair" test is widely used to study antidepressants, mainly on the theoretical assumption that the test animal becomes desperate. In view of the above, we compared behavior of animals subjected to various experimental conditions (4, 15, 30 cm of water), in order to assess whether or not "despair" was the cause of immobility. Our results indicate that the animal's behavior in response to exposure to a dangerous situation, such as that represented by 15 or 30 cm water, depends upon previous knowledge of the environment rather than "despair." We concluded that this test is far from reproducing behavioral changes which characterize depressive illness in humans.
Animals↗
The nonstop transvesical cystometrogram in urethane-anesthetized rats: a simple procedure for quantitative studies on the various phases of urinary bladder voiding cycle.
A new cystometric procedure that involves a nonstop transvesical (through a needle inserted into the bladder dome) infusion of saline in urethane-anesthetized rats is described. This permits the obtainment of a series of repetitive voiding cycles in both male and female rats. Recording at high-chart speed permits quantitative measurements of the various phases of the voiding cycle. Micturition was almost invariably associated with appearance, during a sustained increase of intravesical pressure, of a series of high-frequency oscillations, which were paralleled by a stream-like emission of the infused fluid. Micturition was not observed after topical tetrodotoxin, after bilateral transection of pelvic nerves, or in acute spinal rats. Intravenous hexamethonium produced a dose-related impairment of the voiding cycle, and, at high doses, suppressed micturition, and overflow incontinence ensued. The experimental procedure described herein appears to be suitable for physiopharmacological studies dealing with regulation of voiding cycle.
Anesthesia↗
Effect of temperature on isoprenaline- and barium-induced slow action potentials in guinea-pig ventricular strips.
The effect of variation in temperature (37-32 and 27 degrees C) on electrical and mechanical activity of depolarized and isoprenaline- or barium-reactivated guinea pig ventricular strips was studied. Lowering the temperature brings a marked prolongation of isoprenaline-induced slow action potentials. In addition the maximal rate of depolarization was strongly reduced at lower temperatures. These effects were observed at an extracellular Ca2+ concentration of either 0.9 or 2.5 mM. The accompanying mechanical activities was significantly increased by reduction in temperature. Barium-induced slow action potentials were similarly affected by temperature variations. These observations suggest that hypothermia exert a sort of calcium antagonistic action probably coupled to a reduction of repolarizing outward potassium currents.
Action Potentials↗
Positive inotropic effect of Mg2+ in K+-depolarized isoprenaline-reactivated guinea-pig ventricular strip.
In K+-depolarized isoprenaline-reactivated guinea-pig ventricular strips increase in external Mg2+ concentration produced a biphasic inotropic effect i.e. at low concentrations (2.5-7.5 mM) a slight negative inotropic effect was observed, while at higher Mg2+ concentrations (10-17.5 mM) a strong positive inotropic effect become predominant. Variation in extracellular K+ concentration (17-22 and 25 mM) determined a concentration related reduction in Mg2+-induced positive inotropic effect. Increase in extracellular Ca2+ concentration (2.5-3.6 and 5.4 mM) prevented the development of Mg2+-induced negative inotropic effect but did not affect the magnitude of the positive inotropic effect. Mg2+-induced positive inotropic effect was unaffected by TTX (3 mg/l) and even enhanced by nifedipine (65 nM). Caffeine (0.2-15 mM) antagonized in a concentration dependent manner the positive inotropic effect of Mg2+. On the other hand in the presence of Mg2+ (15 mM) caffeine (0.2 mM) was unable to exert its positive inotropic effect. Mg2+ (15 mM) determined a "Ca2+ entry blocking"--like modifications of electrophysiological parameters of slow action potentials elicited by isoprenaline in K+-depolarized preparations. Such effects of Mg2+ were also present during the positive inotropic effect. The possible mechanisms responsible for these complex inotropic effects of Mg2+ are discussed.
Action Potentials↗
GABA A receptor mediated neurogenic inhibition of motility in the small intestine of urethane-anaesthetized rats.
Intravenous GABA (0.1-3 mg/kg) induced transient relaxation of the duodenum in urethane anaesthetized rats. The effect of GABA was mimicked by homotaurine and antagonized by bicuculline, suggesting the involvement of GABA A receptors in this type of response. Duodenal relaxation induced by GABA was unaffected by i.v. hexamethonium, phentolamine propranolol or 6-hydroxydopamine but was prevented in preparations pretreated with topical tetrodotoxin thus indicating its neurogenic origin. The ability of GABA to induce neurogenic relaxation decreased rapidly when increasing the distance from the duodenum while relaxations induced by DMPP or noradrenaline were observed throughout the whole rat small intestine.
Anesthesia↗
The capsaicin-sensitive innervation of the rat urinary bladder: further studies on mechanisms regulating micturition threshold.
The functional role of the capsaicin-sensitive innervation of the rat urinary bladder in regulating micturition has been investigated by means of the transvesical cystometrogram which allows study of the effects of drugs on the various phases of the bladder voiding cycle in urethane-anesthetized rats. Capsaicin desensitization (50-125 mg./kg., 4 to 60 days before) significantly increased both the volume and pressure threshold for micturition, indicating functional impairment of the mechanisms which transmit volume information from the bladder to the central nervous system. On the other hand the parameters related to the expulsive phase of the voiding cycle of the rat bladder are unaffected by capsaicin pretreatment. In capsaicin-desensitized rats the bladder weight remained within the limits of controls up to 60 days from the treatment although at this time the volume threshold was still elevated. In capsaicin-desensitized rats an increase of infusion rate above the physiological range produced micturition cycles having a normal volume and pressure threshold. These findings suggest that at high values of volume/pressure threshold micturition could be initiated through capsaicin-resistant sensory mechanism(s); in effect, multiple sensory systems, having different thresholds, relay volume/pressure information from the detrusor to the CNS.
Animals↗
The postganglionic excitatory innervation of the mouse urinary bladder and its modulation by prejunctional GABAB receptors.
Field stimulation produced reproducible contractions of the mouse isolated urinary bladder whose amplitude was frequency-related. These contractions were partially sensitive to atropine (3 microM), unaffected by hexamethonium (10 microM) and almost abolished by tetrodotoxin (0.5 microM). Atropine (3 microM) suppressed contractions produced by exogenous acetylcholine thereby indicating atropine-resistance of the nerve-mediated contractions. Nerve-mediated contractions of the mouse urinary bladder were enhanced by physostigmine (0.1-0.5 microM) and inhibited by hemicholinium-3 (0.5 mM) thus confirming the presence of a cholinergic component in the excitatory postganglionic innervation. Atropine (3 microM) inhibition of the nerve-mediated contractions increased with increasing duration and strength of the train of stimulation. The nerve-mediated contractions of the mouse bladder were unaffected by phentolamine (0.2 microM), propranolol (0.3 microM) or indomethacin (5 microM). ATP (1mM) the major candidate for the role of nonadrenergic-noncholinegic (NANC) excitatory neurotransmitter in the mammalian urinary bladder produced a contraction of the mouse isolated bladder. Exposure to the stable ATP analogue alpha, beta-methylene ATP (APCPP) or beta, gamma-methylene ATP (APPCP) produced a partial desensitization of the nerve-mediated response which, for APCPP, was greater in the presence than in the absence of atropine (3 microM). In the presence of atropine (3 microM) and after APCPP desensitization the amplitude of the response to field stimulation amounted to about 20% of the original response and was sensitive to tetrodotoxin, indicating that it is nerve-mediated. GABA (0.001-0.3 mM) inhibited the amplitude of field stimulation induced contractions of mouse urinary bladder. This effect was mimicked by the selective GABAB receptor agonist, (+/-)-baclofen, but not by the selective GABAA receptor agonist, homotaurine. GABA and (+/-)-baclofen exhibited cross-desensitization. The GABA-or (+/-)-baclofen-induced inhibition of the nerve-mediated contractions were reduced by previous exposure to homotaurine (1 mM) or to 5-aminovaleric acid (2 mM), two GABAB receptor antagonists. On the other hand the inhibitory effects of GABA or (+/-)-baclofen were unaffected by picrotoxin (0.1 mM), a selective GABAA receptor antagonist. The inhibitory effect of GABA on nerve-mediated contractions was reduced in the presence of atropine or hemicholinium-3 as well as following desensitization of P2-purinoreceptors.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗