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D Mitolo-Chieppa

Publications and source records attributed to D Mitolo-Chieppa.

At least 37 records · Page 2Linked to original sources
PubMed1992

The effects of (+/-)-idazoxan and its stereoisomers on mouse vas deferens motility in vitro. A comparison with yohimbine.

The effects of idazoxan (IDZ) and its stereoisomers were compared to that of a classical alpha 2-antagonist, yohimbine (YOH), on para-aminoclonidine (PAC)- and norepinephrine (NE)-mediated inhibition of the twitch response evoked in the mouse vas deferens by low-frequency (0.1 Hz) field stimulation. (+/-)-IDZ and (+)-IDZ antagonized the inhibitory effects of PAC, (+)-IDZ being twice as potent as (+/-)-IDZ; in contrast, antagonism by (-)-IDZ failed to meet Schild criteria for a competitive mechanism. YOH completely reversed the inhibition of twitch response induced by NE, but not that induced by PAC; in the latter case, residual inhibition was almost fully reversed by (+)-IDZ and to a lesser extent by (+/-)-IDZ, while (-)-IDZ proved ineffective. These results provide pharmacological evidence of alpha 2-receptor heterogeneity at the vas deferens level. A possible additional mechanism involving imidazoline binding sites is discussed.

Adrenergic alpha-Antagonists↗
PubMed1991

Comparative evaluation of lisuride and terguride, ergot alkaloid derivatives, on the field-stimulated vas deferens of mouse.

The ergot alkaloid derivatives, lisuride (LIS) and terguride (TDHL), known to interact with central dopamine receptors as agonist and partial agonist, respectively, were studied on the field-stimulated mouse vas deferens, where recently the existence of presynaptic dopamine receptors has been evidenced. LIS was a competitive antagonist at prejunctional alpha 2 and DA1 receptors situated on the sympathetic nerve terminals of the mouse, with a pA2 value of 9.2 and 9.1, respectively. LIS was also able to antagonize the effects of LY 171555, selective DA2 agonist, but the type of interaction cannot be conceptualized in terms of competitive antagonism. Likewise, the type of interaction of TDHL with dopaminergic and adrenergic agonist-activated sites is not suggestive of a competitive antagonism. Based on these results, it seems that central and peripheral pharmacologic profiles of LIS and TDHL cannot be overlapped, LIS being a potent DA1- and alpha 2-antagonist with a high degree of specifity for these receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Multiple forms of synaptic coordinative interactions in the autonomic neurotransmission. Tensiometric evaluations in peripheral tissues.

The existence of co-transmitters interacting in the complex regulation of autonomic neurotransmission, has led to investigate the interactive effects between the conventional neurotransmitters and other drugs, such as histamine, serotonin, substance P, strictly related to inflammatory mediators, in both vas deferens and urinary bladder of guinea pig. The results suggest that synergistic interactions, involving post-synaptic sites, exist between co-transmitters; furthermore, inflammatory mediators are able to modify the responses to endogenous (via intramural nerves stimulation) and exogenous conventional neurotransmitters. It is conceivable that inflammatory mediators, released by activation of mast cells either within or delivered to the tissues by the vascular supply, may alter the physiological responses of several organ systems.

Acute-Phase Proteins↗
PubMed1990

Pre-junctional regulation of sympathetic neurotransmission in the mouse vas deferens: assessment of agonist and antagonist potencies.

Dopaminergic agonists and antagonists were tested on the field-stimulated mouse vas deferens. Both LY 171555 and SK & F 38393, relatively selective DA2 and DA1 receptor agonists, respectively, produced concentration-dependent inhibition of the field stimulation-induced contractions, without modifying the baseline tone nor the contractile responses to the exogenous noradrenaline. Both LY 171555 and SK & F 38393 concentration-response curves were shifted rightward in a parallel manner by sulpiride (relatively specific DA2 antagonist) and SCH 23390 (relatively specific DA1 antagonist), respectively. The results are suggestive of the existence of pre-junctional dopamine receptors involved in the regulation of sympathetic neurotransmission in rodent vasa.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

[Effects of the partial dopamine receptor agonist, terguride, on the field-stimulated vas deferens in the mouse].

Transdihydrolisuride (terguride), a 9,10-dihydrogenated analogue of the ergot dopamine agonist lisuride, is characterized as partial dopamine receptor agonist at CNS level. This compound was investigated for its effects on peripheral neurotransmission in the attempt to delineate its pharmacological profile. The contractile responses of field-stimulated mouse vas deferens were slightly inhibited by terguride at very high concentrations (10(-5)-10(-2) M); the selective antagonists for alpha 2-adrenergic and dopamine receptors failed to counteract this effect. Terguride was very effective in blocking the inhibitory effects of LY 171555 (selective DA2 agonist), SK&F 38393 (selective DA1 agonist) and clonidine (selective alpha 2 agonist). In no case the antagonism was competitive: the control dose-response curves were not shifted in a parallel and dose-dependent manner. Therefore terguride displays a mixed DA1, DA2 and alpha 2 antagonistic activity.

Animals↗
PubMed1990

[Multiple receptor interactions in the electrically stimulated ductus deferens of the guinea-pig].

The evidence that ATP is released with noradrenaline as a cotransmitter from sympathetic nerve endings in the isolated guinea-pig vas deferens, had led to investigate the potential interactive effects of P2 and alpha 1 receptors, extending the observations to potentially synergistic interactions of histamine-, acetylcholine- and serotonin-receptors. Ineffective concentrations of histamine, carbachol and serotonin increase the neurogenic response to field stimulation; this effect is prevented by the specific antagonist. The responses to the exogenously applied ATP and noradrenaline are increased as well, suggesting that this synergistic interaction of carbachol is less specific. It can be envisaged that receptor complex is a multicomponent system with subunits specific for the primary neurotransmitter and accessory subunits which may interact to increase the responsiveness of the target cell to simultaneous afferent stimuli.

Adenosine Triphosphate↗
PubMed1989

Interaction between bradykinin and voltage-sensitive sodium channels in myelinated nerve fibers.

The effects of externally and internally applied bradykinin on the excitability of single myelinated nerve fibers were studied. External bradykinin (10 microM) slightly prolongs the action potential of a single myelinated nerve fiber; hence, when the fibers are stimulated by long-lasting pulses, this raises the frequency of repetitive firing in sensory fibers and evokes repetitive activity in motor fibers. Under voltage-clamp conditions, sodium channel inactivation is slowed, while sodium channel activation remains unaffected. Prolonged depolarization of the membrane leads to a maintained sodium current. The voltage dependence of the steady-state sodium current inactivation (h infinity) is shifted in the depolarized direction by approximately 10 mV. Internally applied bradykinin produces a frequency-dependent block of the sodium current. The phenomena described here imply that more than one site on the sodium channel is modified by bradykinin.

Action Potentials↗
PubMed1989

Evidence for the existence of prejunctional receptor sites for dopamine in the mouse vas deferens.

The present work is focused on the effects of newly developed dopaminergic agonists and antagonists on the field-stimulated vas deferens. Both LY 171555 and SK&F 38393, relatively selective DA2 and DA1 receptor agonists, respectively, produced concentration-dependent inhibition of the field stimulation-evoked contractions in the mouse vas deferens; both compounds did not modify the baseline tone nor the contractile responses to exogenous noradrenaline. Control LY 171555 and SK&F 38393 concentration-response curves, were shifted rightward in a parallel manner in the presence of sulpiride (relatively specific DA2 antagonist) and SCH 23390 (relatively specific DA1 antagonist), respectively. Control concentration-response curves for dopaminergic agonists were not modified in the presence of specific blockers for H1 and H2 histamine receptors, serotonin receptors and alpha 2-adrenoceptors. These preliminary findings are suggestive of the existence of two dopaminergic receptor types both presumably located prejunctionally.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1988

Mechanism of action of a structural analog of alphaxalone on myelinated nerve fibre.

The action of alphadolone acetate (0.05-5 mM), a steroid anaesthetic and structural analog of alphaxalone, was investigated on frog myelinated axons under voltage-clamp conditions. When applied externally, alphadolone acetate reduced K and Na currents, with apparent dissociation constants of 0.70 and 1.74 mM, respectively, and without noticeable modification in their time course. In addition, Na conductance-voltage and steady-state inactivation-voltage curves were shifted towards negative voltages. This effect was more pronounced on the steady-state inactivation-voltage relationship. These results suggest that alphadolone acetate blocked K channels indifferently in their resting or open state, and Na channels preferentially in their inactivated state. Alphaxalone has been shown to preferentially block open K and inactivated Na channels (Benoit et al., 1988, Br. J. Pharmacol. 94, 635). Thus, a structural change of a steroid molecule can lead to differences in its mechanism of action. This supports the hypothesis of direct interactions between steroid molecules and target membrane proteins with resulting anaesthetic activity.

Anesthetics↗
PubMed1988

Interactions between molecules of a steroid anaesthetic (alphaxalone) and ionic channels of nodal membrane in voltage-clamped myelinated nerve fibre.

1. The effects of the anaesthetic alphaxalone (0.05 to 1 mM) on the node of Ranvier of isolated myelinated nerve fibres of the frog were studied under voltage-clamp conditions. 2. When added to the solution bathing voltage-clamped nodes, alphaxalone modified neither linear leakage nor capacitative currents but rapidly and reversibly blocked K and Na currents. The blocking effects of the anaesthetic on both types of current were not dependent on the frequency of stimulation of the nerve fibres between 0.7 and 10 Hz. 3. The kinetics of the Na current were not modified by alphaxalone but, in the presence of the drug, the K current showed an apparent fast inactivation. 4. Alphaxalone rapidly and reversibly shifted towards negative voltages both the steady-state K conductance-voltage and the peak Na steady-state inactivation-voltage relationships, without noticeable modification of their shape. In contrast, the anaesthetic reversibly decreased the slope of the peak Na conductance-voltage curve. 5. The reduction of the K current induced by alphaxalone was voltage-dependent with an apparent dissociation constant first decreasing from about 0.25 to 0.08 mM between -20 mV and +20 mV and then remaining constant above +20 mV. In contrast, the apparent dissociation constant for the Na current was almost constant with increasing voltages and equalled about 0.30 mM. Hill coefficient values for both K and Na currents were noticeably less than one. 6. It is concluded that, at higher concentrations than those attainable in the brain or in the plasma during surgical anaesthesia in man, alphaxalone has a 'local anaesthetic-like' action on the peripheral nervous system in that it specifically and differentially interacts with K and Na channel gating systems: it is suggested that the anaesthetic would preferentially modify open K and inactivated Na channels.

Anesthetics↗
PubMed1987

Electrophysiological studies of the effects of the general anaesthetic etomidate on frog myelinated nerve fibre.

The effects of the general anaesthetic etomidate (0.1 to 1 mM) upon the node of Ranvier of frog isolated nerve fibres were investigated under current and voltage clamp conditions. When added to the external solution, etomidate reversibly decreased the amplitude of the action potential. The action potential block, induced by the drug, was reversed by increasing the membrane potential. Etomidate rapidly and reversibly blocked the Na current with an apparent dissociation constant of 0.6 mM. In the presence of the drug, the steady-state inactivation-voltage curve of the Na current was shifted towards negative voltages. The block of Na current by etomidate was partially removed by repetitive depolarization preceded by a 50 ms period of hyperpolarization. In contrast, the block was enhanced when the repetitive depolarization was not preceded by hyperpolarization. This suggests that Na channels were preferentially blocked by the drug in the inactivated state. The K current was reversibly blocked by etomidate with an apparent dissociation constant of 0.2 mM. In the presence of the drug, the K current showed an apparent fast inactivation suggesting that K channels were blocked in the open state. We conclude that at higher concentrations than those attainable in the mammalian brain following single anaesthetic doses the general anaesthetic etomidate has a "local anaesthetic-like' action on the peripheral nervous system.

Action Potentials↗
PubMed1986

Electrophysiological investigation of 2,5-hexanedione neurotoxicity in rats.

Rats were subcutaneously administered 0.8 ml/kg/day 2,5-hexanedione for periods of 18, 25, and 32 days, respectively, and were processed for electrophysiological observations. Action potential and membrane currents were recorded from the sciatic nerve under current- and voltage-clamp conditions. The contractile responses of gastrocnemius and diaphragm muscles following sciatic nerve and phrenic nerve stimulation, respectively, were observed. Animals developing peripheral neuropathy showed hindlimb weakness and depression of body weight gain. Current- and voltage-clamp experiments have shown that after 32 days treatment, the amplitude of the action potential recorded from single myelinated nerve fibers was reduced and the duration was slightly increased; peak sodium current was reduced by 15% and high potassium current density (12 nA) appeared. The twitch responses of diaphragm and gastrocnemius muscles following electrical stimulation of the phrenic and sciatic nerves, respectively, were strongly affected in the 32 day-treated rats. The results are discussed in terms of demyelination which should increase the amplitude of delayed current by exposing potassium channels which under physiological conditions are buried under the myelin sheath.

Action Potentials↗
PubMed1986

Mechanism of action of ketamine in the current and voltage clamped myelinated nerve fibre of the frog.

The effects of the general anaesthetic ketamine, on the frog isolated node of Ranvier, were studied under current and voltage clamp conditions. Ketamine (0.5 and 1 mM) reversibly decreased the amplitude of the action potential and increased both the duration of the action potential and the threshold potential. When the K current was blocked, spontaneous action potentials appeared after washout of the drug. Ketamine rapidly blocked the Na current and more slowly modified a fraction of Na channels (about 10%) to give rise to a non-inactivatable (late) Na current. After washout of the drug, the block reversed more rapidly than the ketamine-induced late Na current disappeared. Steady-state outward, peak Na and ketamine-induced late Na currents were rapidly and reversibly blocked by ketamine with an apparent dissociation constant of 0.7 mM. Both peak Na and ketamine-induced late Na currents were reversibly blocked by procaine.

Action Potentials↗
PubMed1985

Functional evaluation of new experimental model of microsurgical tubulovasostomy in rat.

The function of a new experimental microsurgical model of tubulovasostomy is evaluated. The model is represented by an end-to-end tubulodeferential anastomosis after removal of the proximal (juxtaepididymal) half of the vas deferens and segmental unfolding of the distal part of the epididymal tubule. Both anastomosed segments are evaluated for responsiveness to norepinephrine and field stimulation. The results are discussed in terms of accurate selection of segments to be anastomosed on the basis of their morphofunctional correlates; in fact, it seems worth replacing the segments removed only with others endowed with equivalent properties.

Animals↗