Abnormalities in cough reflex]

Enzymes degrading peptides may participate in the regulation of the cough reflex. Thus, decreases in enzyme activities may enhance cough reflex and a decrease in cough reflex may lead to aspiration pneumonia. Down- and up-regulation of cough reflex is important for the understanding of cough reflex.     

Late Effects of Childhood Acute Leukemia and Its Treatment

Late effects of childhood acute leukemia and its treatment were studied in 766 patients (684 ALL, 73 ANLL, and 9 others) in Japan who had remained in remission for more than 1 year after their first complete remission. Delayed adverse sequelae involve a wide variety of organs and their functions. Short stature was present in 2.61%, obesity in 3.79%, abnormalities of growth hormone secretion in 1.5%, delayed secondary sex characteristics in 1.5% of males and 0.6% of females, motor disturbances in 1.17%, sensory disturbances in 0.91%, intellectual and learning disabilities in 2.48%, abnormal findings in routine neurologic examinations in 1.31%, EEG abnormalities in 4.30%, brain CT abnormalities in 5.09% and cardiac dysfunction in 1.07%. Various other disorders were seen in 20 patients. Many of these delayed adverse sequelae are caused by or related to central nervous system prophylaxis and systemic combination chemotherapy. The results suggest that it is needed to improve therapeutic methods through the stratification of patients by risk factors and detailed analysis of prognostic factors. Moreover it is important to render medical and psychosocial support to long-term survivors of childhood leukemia through interactions between the patient, parents and medical staff.     

Difference between substance P- and acetylcholine-induced currents in mammalian smooth muscle cells.

The effects of substance P (SP) and acetylcholine (ACh) on membrane currents were compared using freshly isolated smooth muscle cells from guinea-pig ileum. Both SP (100 nM) and ACh (10 microM) induced inward currents at negative holding potentials. The ACh-induced current, but not the SP-induced current, showed relaxation upon voltage-stepping. The SP-induced current was increased by hyperpolarization more negative than -50 mV whereas the ACh-induced current was decreased by hyperpolarization. The results suggest that the SP-induced inward current is elicited via an ionic pathway different from that involved with ACh-activated channels.     

Evidence that [3H]glutamate binding sites are masked by biologically relevant endogenous factor on cell membranes of frog spinal cord.

We identified the possible endogenous factor effective to modulate the binding of [3H]-labeled excitatory amino acid agonists and antagonists in the 100,000 x g supernatant of Triton X-100 (0.01%)-treated cell membranes from frog spinal cords. The factor inhibited the binding of [3H]glutamate to Triton X-100-treated cell membranes, to which the binding capacity of [3H]glutamate increased much more than that to intact cell membranes. The binding capacities of [3H]AMPA (an AMPA type agonist) and [3H]CPP (an NMDA type antagonist) to cell membranes remained low by Triton treatment, but they were enhanced significantly by the addition of the factor. The effect of the factor on the [3H]kainate binding was hardly observable. The factor may provide key information on receptor structures and the classification of receptor types concerning excitatory amino acids in the mammalian central nervous system.     

Characterization of inhibition by haloperidol and chlorpromazine of a voltage-activated K+ current in rat phaeochromocytoma cells.

1. Inhibition by haloperidol and chlorpromazine of a voltage-activated K+ current was characterized in rat phaeochromocytoma PC12 cells by use of whole-cell voltage-clamp techniques. 2. Haloperidol or chlorpromazine (1 and 10 microM) inhibited a K+ current activated by a test potential of +20 mV applied from a holding potential of -60 mV. The K+ current inhibition did not exhibit voltage-dependence when test potentials were changed between -10 and +40 mV or when holding potentials were changed between -120 and -60 mV. 3. Effects of compounds that are related to haloperidol and chlorpromazine in their pharmacological actions were examined. Fluspirilene (1 and 10 microM), an antipsychotic drug, inhibited the K+ current, but pimozide (1 and 10 microM), another antipsychotic drug did not significantly inhibit the K+ current. Sulpiride (1 or 10 microM), an antagonist of dopamine D2 receptors, did not affect the K+ current whereas (+)-SCH-23390 (10 microM), an antagonist of dopamine D1 receptors, reduced the K+ current. As for calmodulin antagonists, W-7 (100 microM), but not calmidazolium (1 microM), reduced the K+ current. 4. The inhibition by haloperidol or chlorpromazine of the K+ current was abolished when GTP in intracellular solution was replaced with GDP beta S. Similarly, the inhibition by pimozide, fluspirilene, (+)-SCH-23390 or W-7 was abolished or attenuated in the presence of intracellular GDP beta S. The inhibition by haloperidol or chlorpromazine was not prevented when cells were pretreated with pertussis toxin or when K-252a, an inhibitor of a variety of protein kinases, was included in the intracellular solution. 5. Haloperidol and chlorpromazine reduced a Ba2+ current permeating through Ca2+ channels. Inhibition by haloperidol or chlorpromazine of the Ba2+ current was not affected by GDP beta S included in the intracellular solution. 6. It is concluded that haloperidol and chlorpromazine inhibit voltage-gated K+ channels in PC12 cells by a mechanism involving GTP-binding proteins. The inhibition may not be related to their activity as antagonists of dopamine D2 receptors or calmodulin antagonists.