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Biomedical subjects

C A Maggi

Publications and source records attributed to C A Maggi.

At least 541 records · Page 30Linked to original sources
PubMed1986

Analysis of factors involved in determining urinary bladder voiding cycle in urethan-anesthetized rats.

The mechanism(s) involved in determining the voiding cycle of the rat urinary bladder have been investigated in urethan-anesthetized animals. Fluid emission is almost confined to that phase of the voiding cycle which is characterized by the presence of a series of high-frequency oscillations in intraluminal pressure (IPHFO). During this phase the mean urethral flow rate reached a maximum and fluid was expelled in a stream-like fashion. The index obtained by multiplying the amplitude of IPHFO by their duration was significantly related to the maximal value of urethral flow rate. The IPHFO were selectively abolished by administration of d-tubocurarine at a dose that barely affects detrusor contractility. Moreover, d-tubocurarine reduced mean urethral flow rate and increased residual volume. The reflex (hexamethonium sensitive) mechanism(s) responsible for the generation of IPHFO is more developed in male than female rats. This mechanism, which involves activation of skeletal muscle, plays a significant role in determining bladder voiding in this species.

Anesthesia↗
PubMed1986

Rociverine citrate: a new spasmolytic agent, potentially useful in the treatment of urinary bladder hyperreflexia.

Rociverine citrate was evaluated for its ability to affect the motility of rat urinary bladder, in vitro and in vivo, in comparison with flavoxate hydrochloride. Rociverine counteracted both methacholine- and high K+-induced tonic contractions of bladder strips. In anaesthetized rats, intravenous rociverine inhibited dose-dependently frequency and amplitude of the distension-induced rhythmic contractions (DIRCs) of urinary bladder and counteracted the topical high K+-induced pressure increase in the same organ. Orally administered rociverine produced a dose-related reversal of the reserpine-induced detrusor hyperreflexia in anaesthetized rats. In each of these experimental models rociverine was more effective than flavoxate. These results point to the usefulness of rociverine in the treatment of urinary bladder motility disorders.

Animals↗
PubMed1986

Activation of micturition reflex by substance P and substance K: indirect evidence for the existence of multiple tachykinin receptors in the rat urinary bladder.

The ability of substance P (SP) and substance K (SK) to activate motility of the rat urinary bladder "in vivo" and "in vitro" have been compared. In urethane-anesthetized rats topical application of tachykinins on the serosal surface of the bladder elicited a series of neurogenic rhythmic contractions (micturition reflex). SK is about 13.5 times more potent than SP. The extent of the effects of both SP and SK depends on the bladder initial volume. SP and SK are equally effective in: contracting the tetrodotoxin-pretreated rat bladder in vivo; contracting the isolated rat bladder in vitro; enhancing the contractions induced by field stimulation; and delaying relaxation of bladder muscle in response to stretch. These findings suggest the existence of two different sites (receptors) for tachykinins in the rat bladder whose activation is responsible for initiation of the micturition reflex and direct smooth muscle contraction, respectively. The higher potency of SK, as compared to SP, in activating the micturition reflex suggests the involvement of a receptor of the SP-E type, possibly located on the afferent nerve endings, in the mediation of this type of response. The other receptor, located on the smooth muscle cell (and possibly on the efferent nerve endings) appears to be of the SP-P type, as it is equally sensitive to the two tachykinins.

Administration, Topical↗
PubMed1986

Motor effect of neurokinins on the rat duodenum: evidence for the involvement of substance K and substance P receptors.

The motor effects of kassinin (KAS), substance P (SP) or neurokinin A (NKA) on rat duodenum have been investigated in vivo (urethane anesthesia) or in vitro. Intravenous neurokinins produced a phasic contraction of the duodenum that was unaffected by atropine, hexamethonium or tetrodotoxin. KAS, NKA and SP were almost equieffective in producing this phasic contraction. In addition KAS and NKA (but not SP) induced a tonic contraction with a superimposed series of rhythmic contractions. SP did not produce tonic or rhythmic contractions even in doses producing maximal effects on blood pressure. The KAS-induced tonic and rhythmic contractions were unaffected by atropine or hexamethonium and potentiated markedly by tetrodotoxin. Similar findings were obtained after topical application of neurokinins on the outer surface of the duodenum in vivo or recording the mechanical response of the longitudinal muscle in vitro. The phasic component of the KAS- or SP-induced contraction was reduced selectively, both in vivo and in vitro by [D-Pro2,D-Trp7,9]SP, an SP antagonist. It is concluded that two types of receptors mediate the motor effects of neurokinins in the rat duodenum, one of which is of the SP-P type and is mainly involved in producing the phasic contraction. The other receptor is of the SP-K type and mediates mainly the tonic contraction.

Animals↗
PubMed1985

Further evidence for involvement of adenosine-5'-triphosphate in non-adrenergic non-cholinergic relaxation of the isolated rat duodenum.

The nature of the inhbitory non-adrenergic non-cholinergic (NANC) neurotransmitter responsible for neurogenic relaxation of rat duodenum was studied with in vitro techniques. Adenosine 5'-triphosphate (ATP)(1 mM), gamma-aminobutyric acid (GABA, 1 mM), dimethylphenylpiperazinium (DMPP, 0.1 mM) and field stimulation (60 V, 2 ms, 0.1 Hz) produced transient relaxation followed by rebound contraction. In contrast vasoactive intestinal polypeptide (VIP) (0.3 microM) and noradrenaline (1 microM) induced relaxation which set in more slowly and lasted longer. Tetrodotoxin (0.85 microM) abolished field stimulation-induced relaxation but not ATP-, VIP- or noradrenaline-induced relaxation. Nucleotide pyrophosphatase (0.25 U/ml), but not the proteolytic enzyme alpha-chymotrypsin (2 U/ml), selectively antagonized NANC relaxation. The rank order of potency of various adenine derivatives for inducing relaxation was adenosine-5'-triphosphate greater than adenosine-5'-diphosphate much greater than adenosine greater than adenosine-5'-monophosphate. ATP-induced relaxation was selectively antagonized by the putative P2 purinoceptor antagonist reactive blue 2, but unaffected by the selective P1 purinoceptor antagonist 8-phenyltheophylline. The duration of ATP- as well as beta-gamma-methylene adenosine-5'-triphosphate (a stable analogue of ATP)-induced relaxation was similar and was unaffected by indomethacin 10 microM (which abolished the rebound contraction). In those preparations whose contractile tone was increased by using a high-K+ medium the ability of ATP to elicit relaxation was markedly reduced, while GABA- and DMPP-induced relaxation was abolished. On the other hand, ATP-, GABA- and DMPP-induced relaxation of the tonic component of 5-hydroxytryptamine (5-HT)(0.1 mM)-induced contraction was similar to that observed in control conditions. These findings add further weight to the proposal that endogenous ATP is involved in determining NANC relaxation of rat duodenum.

Adenosine↗
PubMed1985

Comparison of the effects of substance P and substance K on blood pressure, salivation and urinary bladder motility in urethane-anaesthetized rats.

The effects of substance P and substance K on blood pressure, salivation and urinary bladder motility were investigated in urethane-anaesthetized rats. On intravenous administration, both peptides produced dose-related reductions in blood pressure, substance P being 25-30 times more potent than substance K. Substance P induced a dose-dependent increase of salivation, while substance K was half as active and induced only 40% of the maximum effect of substance P. The two tachykinins induced contractions of the urinary bladder, substance K being about twice as effective as substance P. Substance K was more effective than substance P in activating micturition. These findings provide further evidence that multiple receptor types are involved in mediating the effects of tachykinins in peripheral organs.

Anesthesia↗
PubMed1985

The effect of peripherally administered GABA on noradrenaline-induced reflex vagal bradycardia in urethane anaesthetized rats.

Intravenously administered GABA significantly reduced the size of noradrenaline-induced reflex vagal bradycardia without affecting blood pressure increase. Intravenously administered GABA reduced bradycardia elicited by stimulation of preganglionic fibres in the vagus nerve. These findings provide evidence suggesting that, in addition to its well known effects on structures regulation cardiovascular function at CNS level GABA could modulate baroreceptor reflex(es) by acting at a peripheral site.

Anesthesia↗
PubMed1985

The effect of cyclooxygenase inhibitors on the low filling rate cystometrogram in urethane anesthetized rats.

The effect of two widely used cyclooxygenase inhibitors (indomethacin and ketoprofen) on the low filling rate cystometrogram was investigated in urethane anesthetized rats. Both indomethacin and ketoprofen significantly increased volume threshold to elicit neurogenic bladder contractions without affecting their amplitude. Also the pressure threshold was unaffected by both drugs while the volume/pressure relationship was significantly flattened compared to controls. These findings indicate that acute suppression of arachidonic acid metabolism along the cyclooxygenase pathway increases the micturition threshold without affecting bladder muscle contractility and/or neurotransmission along the efferent pathway of the micturition reflex.

Anesthesia↗
PubMed1985

The effect of capsaicin pretreatment on the cystometrograms of urethane anesthetized rats.

Administration of capsaicin to newborn rats produced a slight but significant increase in bladder weight and markedly altered the cystometrograms of urethane anesthetized rats. In particular capsaicin pretreatment significantly increase micturition threshold. In many of these preparations the bladders exhibited a hypertonic response to saline filling; the flat phase of the cystometrogram was not observed. Capsaicin pretreatment of adult animals increased micturition threshold up to 1 month from capsaicin administration. In these preparations a flat volume-pressure relationship preceded micturition contractions. Administration of capsaicin to both newborn and adult animals did not alter the amplitude of micturition contractions. Intravesical installation of capsaicin had an acute excitatory effect on the responsiveness of the urinary bladder to reflex activation. These findings indicate that capsaicin pretreatment produces a functional impairment of the sensory branch of micturition reflexes and suggest that a capsaicin-sensitive mechanism(s) is involved in the regulation of micturition threshold.

Anesthesia, General↗
PubMed1985

Dual effect of GABA on the contractile activity of the guinea-pig isolated urinary bladder.

The effects of GABA and related substances were examined in isolated detrusor strips from the dome of the guinea-pig urinary bladder. GABA (0.01-1 mM) produced concentration-related phasic contractions of isolated strips from the guinea-pig urinary bladder dome. This effect of GABA was mimicked by homotaurine and muscimol, selective GABAA receptor agonists but not by (+/-)-baclofen, a selective GABAB receptor agonist. A specific cross desensitization was observed between GABA, homotaurine and muscimol but not between (+/-)-baclofen and GABA. GABA (1 mM)-induced contractions were antagonized by picrotoxin, a selective GABAA receptor antagonist. GABA-induced contractions were almost abolished by tetrodotoxin (0.5 microM, TTX) thus indicating their neurogenic origin. In addition GABA-induced contractions were partially antagonized by atropine (to about the same extent as those produced by dimethylphenylpiperazinium (DMPP), a ganglionic stimulant), but were unaffected by hexamethonium (10 microM), phentolamine (0.2 microM) or indomethacin (5 microM). In the presence of GABA the contractile effect of both DMPP (TTX-sensitive) and acetylcholine (ACh, TTX-insensitive) were significantly reduced. Similar findings were obtained with DMPP, i.e. in preparations exposed to this ganglionic stimulant both GABA- and ACh-induced contractions were depressed. Homotaurine but not (+/-)-baclofen mimicked the depressant effect of GABA on DMPP-induced contractions. The depressant effect of GABA on ACh-induced contractions of the guinea-pig urinary bladder was neurogenic in origin, i.e., was not observed in preparations exposed to TTX. These experiments indicate that GABA has a dual effect on the contractile behaviour of the guinea-pig isolated urinary bladder. Recently it has been proposed that endogenous GABA plays a neuromodulatory role in this organ. Our data suggest that in the early phase of neurogenic activation of detrusor muscle (micturition reflex) GABA might transiently enhance excitatory neurotransmission followed by a more sustained inhibition of contractility.

Acetylcholine↗
PubMed1985

Contribution of neurogenic and myogenic factors to the contractile activity of the guinea-pig distal colon in vivo and in vitro.

The response of the guinea-pig distal colon to distension and drugs expected to interfere with neural control of contractile activity were investigated in urethane anaesthetized animals and compared to results obtained in the isolated preparation. Under urethane anaesthesia bout 50% of the unloaded preparations had no detectable contractile activity. However these preparations contracted in response to topical acetylcholine. Saline distension induced the appearance of a phasic contractile activity in 'quiescent' preparations and enhanced amplitude of contractions in previously active ones. Atropine (1 mg/kg i.v.) reduced tone and transiently suppressed phasic contractile activity of the distal colon. When phasic contractile activity resumed a second dose of atropine had no further inhibitory effect. Topical physostigmine (20 micrograms in 0.1 ml) produced a marked and long lasting increase in tone paralleled by a marked enhancement in amplitude of the phasic contractile activity. These excitatory effects of topical physostigmine were suppressed by intravenous atropine (1 mg/kg). Hexamethonium (20 mg/kg i.v.) produced a sudden and transient increase in tone and suppressed DMPP (0.1 mg/kg i.v.) but not noradrenaline (2 micrograms/kg i.v.) induced relaxations. Propranolol (2 mg/kg i.v.) or phentolamine (0.5 mg/kg i.v.) transiently increased tone of the guinea-pig distal colon and suppressed noradrenaline induced relaxations. DMPP induced relaxations were reduced by propranolol plus phentolamine. Topical tetrodotoxin (50 micrograms in 0.1 ml) had an overall slight excitatory effect on phasic contractile activity of the in vivo preparation. The effects of i.v. atropine, hexamethonium, phentolamine or propranolol on tone and spontaneous activity were prevented by pretreatment with tetrodotoxin. Isolated segments of guinea-pig distal colon exhibited a fairly regular spontaneous phasic contractile activity whose amplitude was increased by stretching of the preparation. Atropine (3 microM) produced a transient inhibition while hexamethonium (40 microM) had no effect on spontaneous contractile activity. Tetrodotoxin (0.5 microM) had both inhibitory and excitatory effects on tone and spontaneous activity of the preparation. At steady state amplitude of contractions was enhanced (15-30% increase) by tetrodotoxin. DMPP (1-100 microM) first induced a phasic contraction and then suppressed transiently the spontaneous activity of the isolated preparation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Pharmacological evidence for the existence of two components in the twitch response to field stimulation of detrusor strips from the rat urinary bladder.

Isolated strips from the anterior dome of the rat urinary bladder respond to single pulse field stimulation with a contraction. Two distinct components of this contraction ("early' and "late') could be observed, both of which were unaffected by hexamethonium (10 microM) and almost abolished by tetrodotoxin (1 microM) indicating their dependence on neurotransmitter release from postganglionic nerve endings. Atropine (3 microM) inhibited the "late' component (over 60%) to a significantly greater extent than the "early' component (less than 10%) Amplitude of the "early' component was usually greater than that of the "late' component. There was almost no difference between the "early' and "late' component in respect of their relationship to stimulus strength and pulse duration. Physostigmine (0.03 microM) enhanced both components of the nerve-mediated contraction, although enhancement of the "late' component was much greater than that of the "early' one. Tetraethylammonium (TEA, 0.5-5 mM) enhanced, in a concentration-related manner, both "early' and "late' components of the nerve-mediated contraction. Following exposure to physostigmine or TEA (5 mM) both "early' and "late' components of contraction were almost completely inhibited by tetrodotoxin. Atropine inhibition was more evident on the "late' as compared to "early' component of contraction. These findings demonstrate the presence, in the twitch response of rat isolated urinary bladder to field stimulation, of two nerve-mediated components which exhibit a different susceptibility to atropine and physostigmine.

Animals↗
PubMed1985

GABAA and GABAB receptors in detrusor strips from guinea-pig bladder dome.

The effects of various GABAA and GABAB receptor agonists and antagonists on electrically induced contractions of detrusor strips from guinea-pig urinary bladder dome were investigated by using both supra and submaximal parameters of stimulation. In supramaximally stimulated preparations GABA (1 mM) inhibited amplitude of contractions. This effect was mimicked, to a lesser degree, by the selective GABAB receptor agonist, (+/-)-baclofen (0.1 mM). Exposure to (+/-)-baclofen reduced markedly the effects of a subsequent challenge with GABA. The GABAA receptor agonists, muscimol (0.3 mM) and homotaurine (1 mM), produced a slight inhibition of contractions and reduced the effects of a subsequent challenge with GABA. The selective GABAA receptor antagonist, picrotoxin (0.1 mM), had a slight, but significant, antagonistic effect toward GABA, but had no effect against (+/-)-baclofen. GABA inhibition of supramaximally stimulated contractions was partly reduced by previous exposure to atropine (3 microM) or to the putative P2-purinoreceptor antagonist, reactive blue 2 (0.3 mM) as well as by desensitization of P2-purinoreceptors produced by the stable ATP analogue beta-gamma-methylene ATP (APPCP). GABA inhibition was unaffected by phentolamine (0.2 microM), propranolol (0.3 microM) or hexamethonium (10 microM). The inhibition produced by atropine plus reactive blue 2 or APPCP desensitization was additive or more than additive. In submaximally stimulated preparations GABA (0.01-1 mM) produced a transient, concentration related enhancement of amplitude of contractions. This effect was mimicked by either muscimol (0.3 mM) or homotaurine (1 mM) but not by (+/-)-baclofen (0.1 mM). A cross desensitization could be observed between the effects of muscimol or homotaurine on one hand and GABA on the other, but not between (+/-)-baclofen and GABA. Picrotoxin (0.03-0.1 mM) produced a concentration dependent antagonism of a noncompetitive type against the excitatory effect of GABA in submaximally stimulated preparations. Previous exposure to either atropine (3 microM), phentolamine (0.2 microM) or hexamethonium (10 microM) failed to affect GABA induced enhancement of submaximally stimulated contractions. On the other hand the effects of GABA were reduced by reactive blue 2 (0.1-0.9 mM) or by desensitization of P2-purinoreceptors. In preparations exposed to tetrodotoxin (TTX, 0.3 microM), field stimulation induced contractions are attributable to a direct excitation of smooth muscle cells. Under these conditions GABA (1 mM) was ineffective, indicating that, in the absence of TTX, it affects the excitability of neural elements in the bladder wall.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

5-Aminovaleric acid interactions with GABAA and GABAB receptors in guinea-pig ileum.

The potential interaction of 5-aminovaleric acid (5-AVA) on GABAA and GABAB receptors was investigated on the guinea-pig isolated ileum myenteric plexus preparation. In the unstimulated preparation 5-AVA (0.1-3 mM) produced a transient contraction which was abolished by previous exposure to picrotoxin (0.1 mM), atropine (3 microM) or tetrodotoxin (0.3 microM). Cross desensitization was observed between the contractile effects of 5-AVA and GABA, while a previous exposure to (+/-)-baclofen did not affect 5-AVA induced contractions. 5-AVA antagonized the relaxant effect of (+/-)-baclofen in unstimulated preparations. 5-AVA (1 mM) had no effect on amplitude of twitches in supramaximally stimulated preparations while GABA produced a concentration related inhibition. In the presence of 5-AVA (1 mM) the concentration response curve to GABA was shifted to the right without a reduction of the maximal effect attainable. These observations indicate that 5-AVA interacts with both GABAA and GABAB receptors in guinea-pig ileum. The concentrations required to observe a GABAA effect are of the same order as those which are effective in producing a blockade of GABAB mediated responses.

Amino Acids↗
PubMed1985

Modulatory activity of GABAB receptors on cholinergic tone in guinea-pig distal colon.

The effect of gamma-aminobutyric acid (GABA) administration was studied in both in vitro and in vivo preparations of the guinea-pig distal colon. In in vitro preparations GABA (10(-7) - 10(-3) M) elicited a dose-dependent relaxation; a decrease in the spontaneous contractions was sometimes observed. The effect of GABA was mimicked by (-)-baclofen, which gave a dose-response curve overlapping that of GABA, while (+)-baclofen was about one hundred times less potent. The relaxation responses induced by the above drugs were antagonized by 5-aminovaleric acid (5 X 10(-4) M), which did not affect adenosine-induced relaxation, but they were insensitive to bicuculline (10(-5) M) and picrotoxin (10(-5) M). Moreover, they were prevented by tetrodotoxin (6 X 10(-7) M). In hyoscine (10(-7) M)-pretreated preparations, GABA still evoked a small relaxation response (approx. 10% of the maximum) that was bicuculline-sensitive. Desensitization to GABA (10(-5) M) was observed. A specific cross-desensitization occurred between GABA (10(-5) M) and (-)-baclofen (10(-5) M). In in vivo preparations, GABA (10 mumol kg-1) and (-)-baclofen (5 mumol kg-1) produced a dose-related inhibition of basal tone, while (+)-baclofen (5 mumol kg-1) had much less effect (about 25%). A decrease in the spontaneous contractions was sometimes observed. The relaxant effect of GABA and (-)-baclofen persisted in guinea-pigs pretreated (1-2 min) with picrotoxin (1.6 mumol kg-1), whereas it was significantly reduced in animals injected 1 min beforehand with 5-aminovaleric acid (0.2 mmol). The maximal relaxant effect induced by GABA and (-)-baclofen did not differ from that of atropine (0.9 mumol kg-1) and after atropine administration GABA had no further inhibitory effect. Relaxation responses induced by GABA and (-)-baclofen still occurred after blockade of nicotinic receptors by hexamethonium (0.17 mmol kg-1), which itself caused an increase in the basal tone. When the tone was increased by topical application of physostigmine (40 micrograms), GABA and (-)-baclofen induced a greater relaxation than that obtained in basal conditions. It is concluded that GABA, both in vitro and in vivo administration, inhibits cholinergic tone in guinea-pig distal colon and that this effect is mediated mainly by activation of GABAB receptors. Further experiments are required to ascertain the possible physiological role of a GABA-releasing neuronal system in the colon in vivo.

Amino Acids↗
PubMed1985

Intracisternal glycine activates the micturition reflex in urethane-anaesthetized rats.

Intracisternal glycine, but not GABA, activates a series of neurogenic rhythmic contractions of the urinary bladder in urethane-anaesthetized rats. This effect of glycine was prevented by strychnine but not by bicuculline, indicating the involvement of specific glycinergic receptors. The effects of glycine were also prevented by either atropine or haloperidol suggesting an involvement of cholinergic and monoaminergic excitatory neurotransmission to the bladder.

Anesthesia↗