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  • 5-HT3 Receptor antagonism  (1)
  • Ca channel  (1)
  • Ca2+ channel  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 344 (1991), S. 564-567 
    ISSN: 1432-1912
    Keywords: Vomiting ; 5-HT ; 2-Me-5-HT ; 5-HT3 Receptor antagonism ; Cancer Chemotherapy ; House musk shrew (Suncus murinus)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The emetic effects of 5-hydroxytryptamine (5-HT) and 5-HT3 receptor agonists were investigated in the house musk shrew, Suncus murinus. 5-Hydroxytryptamine (5-HT; i.p., i.v., s.c.) and 2-methyl-5-HT (2-Me-5HT; i.p.) but not 5-hydroxyindoleacetic acid (i.p.) or 5-ethoxytryptamine (i.p.) induced emesis with very short latency. Tropisetron (ICS 205-930, a 5-HT3 receptor antagonist, s.c.) blocked the emesis induced by 5-HT (10 mg/kg, i.p.) and 2-Me-5-HT (5 mg/kg, i.p.) with respective ID50 values of 7.8 and 70.9 μg/kg. Pindolol (5-HT1 receptor antagonist) and ketanserin (5-HT2 receptor antagonist) were about 100 times less potent than tropisetron. The emesis induced by 5-HT was prevented by surgical vagotomy but not by pretreatment with a combination of atropine (0.1 mg/kg, s.c.) and hexamethonium (10 mg/kg, s.c.). These results clearly indicate that 5-HT is emetogenic probably through a stimulation of peripheral 5-HT3 receptors.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 346 (1992), S. 515-522 
    ISSN: 1432-1912
    Keywords: Calcitonin gene-related peptide ; Smooth muscle cells ; Vas deferens - Membrane currents ; Ca2+ channel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Effects of calcitonin gene-related peptide (CGRP), a putative non-adrenergic non-cholinergic neutrotransmitter on the electrical properties of the cell membrane, were investigated in enzymically dispersed smooth muscle cells from rat vas deferens. Under current clamp conditions, CGRP (up to 10−7 M) did not induce significant changes in membrane potentials or input resistance in the resting state. The configurations of action potentials elicited by depolarizing current pulses were also unaffected, except that a prolongation of the duration of the action potentials by a high dose (10−7 M) of CGRP was observed in some of the cells. Under whole cell voltage clamp conditions, the transient and sustained K+ currents, activated by depolarizing voltage-steps, were apparently decreased in the presence of 10−9 to 10−7 M CGRP. The peptide increased the voltage-gated Ca2+ current in cells loaded with 145 mM Cs+ solution in order to block the K+ currents. The voltage-dependency of the peak Ca2+ current was not changed by CGRP. Ba2+ (10.8 mM) was used as a charge carrier for the Ca2+-channel current to clarify further the effects of CGRP on the properties of the current. CGRP (10−8 M) delayed the inactivation time course of the Ca2+-channel current and slowed the recovery from inactivation. The peptide did not affect the steady-state inactivation measured by changing the holding potential. The Ca2+-channel current in the presence of CGRP was suppressed by nicardipine (10−6 M) to the same extent as the current under control conditions. The results suggest that CGRP modifies the L-type Ca2+ channel in smooth muscle cells.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 100 (1987), S. 13-19 
    ISSN: 1432-1424
    Keywords: smooth muscle cells ; Ca channel ; whole cell recording ; inactivation ; Ca dependency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Ca-channel currents were recorded in Cs-loaded single smooth muscle cells from rat vas deferens to define the dependence of the inactivation time course on Ca concentration. The decay of Ca-channel current obtained in a Ba2+- or Sr2+-containing external solution during long voltage-clamp pulses was much slower than that in a Ca-containing solution. The difference was not due to a change in the surface potential of the membrane as judged from the steady-state activation and inactivation curves. When Ca was the charge carrier, increasing external Ca concentration slightly accelerated the rate of inactivation. In addition, the rate of inactivation of Ca-channel current in 10.8mm Ba was also accelerated by adding Ca to the external solution in a concentration-dependent manner. The time course of Ca-current inactivation was slowed when the cells were dialyzed with a high concentration of citrate, a Ca-chelating agent. From these results, we concluded that a mechanism regulated by intracellular Ca activity plays a role in the inactivation of Ca channels in smooth muscle. The Ca-dependent process may protect against Ca overload by regulating Ca entry in smooth muscle cells.
    Type of Medium: Electronic Resource
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