Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracellular recordings were made from neurones in the myenteric plexus of the guinea-pig ileum. Presynaptic nerves were excited by a focal stimulating electrode on an interganglionic strand. Fast excitatory postsynaptic potentials (e.p.s.ps) were depressed in amplitude by morphine and [Met5]enkephalin in the concentration range of 1 nM-1 microM. Nicotinic depolarizations evoked by exogenously applied acetylcholine (ACh) were not affected by these opioids. Hyperpolarization of the presynaptic fibres probably contributed to the depression of the fast e.p.s.p. because fast e.p.s.ps evoked by low stimulus voltages were more depressed than those evoked by high stimulus voltages and fast e.p.s.ps resulting from activation of a single presynaptic fibre were blocked in a non-graded manner. Opioids depressed the slow e.p.s.p. in those neurones in which they did not change the resting membrane potential. The slow e.p.s.p. was increased in amplitude in those neurones hyperpolarized by opioids. Depolarizations resulting from application of barium, substance P or ACh were also enhanced by opioids. Equivalent circuit models in which opioids increase, and substance P or ACh decrease, the same potassium conductance could account for this enhancement. The actions of opioids were prevented or reversed by naloxone (1 nM-1 microM). It is concluded that morphine and enkephalin inhibit the release of ACh and a non-cholinergic transmitter from fibres of the myenteric plexus, and that this may involve a hyperpolarization of presynaptic fibres. Additionally, opioids can interact postsynaptically with other substances which affect membrane potassium conductances.
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PMID:Opioid inhibition of synaptic transmission in the guinea-pig myenteric plexus. 241 22

Right ventricular strips from guinea pig hearts were used to study the interaction between norepinephrine (NE) and the Ca2+ channel blockers nifedipine and verapamil on maximal upstroke velocity (Vmax) of rapid depolarization in potassium-depolarized preparations. Barium ion (0.8 mM) was added to the bathing solution to restore excitability of the K+-depolarized tissue. Concentrations of verapamil (5 X 10(-7) M) and nifedipine (5 X 10(-8) M) were selected to produce optimal depression of Vmax under both tonic (rested) and phasic (pacing frequencies from 0.05 to 2.0 Hz) conditions. NE increased the tonic and phasic Vmax of control preparations in equal proportion at all stimulation frequencies. Thus, the physiological frequency dependence of Vmax was not altered by NE. NE (10(-6) M) produced an increase of 11.8 +/- 2.2% in the tonic Vmax of verapamil-treated preparations and an increase of 17.4 +/- 1.1% in the tonic Vmax of nifedipine-treated preparations. In each case the enhancement of Vmax by NE was proportional for both tonic and phasic conditions, thus showing no effect on the frequency-dependent action of either drug. In all cases, the NE-induced increase in Vmax was concentration dependent. Higher concentrations of NE thwarted the measurement of tonic Vmax due to the onset of spontaneous activity except in the presence of nifedipine (5 X 10(-8) M). The maximal concentration of NE that could be tolerated without the onset of spontaneous activity was directly related to the degree of tonic depression of Vmax induced by the Ca2+ channel blocking agent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of norepinephrine on the tonic and phasic depression of Vmax by nifedipine and verapamil in guinea pig ventricle. 242 18

Effects of pentobarbital on the calcium current of Aplysia neurons were investigated under current- and voltage-clamp conditions using the conventional two-microelectrode technique. Pentobarbital attenuated the progressive broadening of repeated action potentials of somata, suggesting a reduction in the calcium current. When calcium ion was replaced with barium ion in the perfusing solution, in which neither sodium nor potassium ions carried transmembrane currents, the barium current (IBa) which flowed through the calcium channel of the cell membrane was generated by depolarizing pulses of several hundred milliseconds applied every 1 min from a holding potential of -50 mV. The IBa was not affected by tetrodotoxin (30 microM). The current was decreased by pentobarbital (0.1-5 mM) in a dose-dependent manner. The inhibition was much greater at a lower pH of the perfusate, indicating that the uncharged form of the agent was responsible. The voltage-dependent inactivation of the IBa proceeded with two time constants [190 +/- 21 and 2020 +/- 146 msec (N = 4) at -10 mV], both of which were shortened by adding 1 mM pentobarbital [to 120 +/- 18 and 540 +/- 51 msec (N = 4), respectively]. The IBa recovered from the inactivation with two time constants [60 +/- 7 and 871 +/- 76 msec (N = 3) at -50 mV]. The anesthetic (1 mM) prolonged both of them, to 124 +/- 20 and 1480 +/- 172 msec (N = 3), respectively, resulting in a use-dependent depression of the current at 2-Hz stimulation. Pentobarbital reduced the IBa to a greater extent when the holding potential was more positive (-30 instead of -50 mV), indicating a higher affinity of the drug to the inactivated state of the channel. These findings suggest that the attenuation of the progressive broadening of successive spikes by pentobarbital is due to a decrease in the voltage- and time-dependent calcium current, ending in depression of transmitter release from the nerve terminal.
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PMID:Reduction of the voltage-dependent calcium current in Aplysia neurons by pentobarbital. 243 43

Right ventricular strips from guinea pig hearts were used to compare the effects of nifedipine and verapamil on the maximal upstroke velocity (Vmax) of rapid depolarization in potassium-depolarized preparations. The Vmax was used as an indirect measure of the slow inward current (Isi). Barium (0.8 mM) was added to the Tyrode solution to restore excitability of the K-depolarized tissue. The effects of nifedipine and verapamil on rested state Vmax (VmaxRS), frequency-dependent changes in Vmax, and recovery of Vmax as a function of diastolic interval were studied. The depression of Vmax at rested state (RS), following 3-5-min rest, was concentration-dependent for both drugs, although the effect of nifedipine was greater. The percentage depression of VmaxRS by nifedipine was 24.3 +/- 6.4 at 10(-8)M, 51.3 +/- 2.6 at 5 X 10(-8)M, and 74.0 +/- 1.0 at 10(-7)M. For verapamil the values were 6.2 +/- 3.8 at 10(-7)M, 13.1 +/- 0.9 at 5 X 10(-7)M, and 42.0 +/- 0.5 at 10(-6)M. The depression of Vmax by each drug was frequency-dependent over a range from 0.05 to 2.0 Hz. Frequency-dependence was quantitatively greater with verapamil. The kinetics of recovery of Vmax were assessed by means of paired stimuli given at varying diastolic intervals during recovery from a RS depolarization. The recovery curve was biexponential. In the drug-free condition, the time constant for the first phase of recovery (Tr1) was 140 +/- 12 ms and the time constant for the second phase (Tr2) was 2689 +/- 146 ms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Frequency-dependence of Vmax in K-depolarized guinea pig ventricle: effects of nifedipine and verapamil. 258 Jan 43

A case of a IIa + IIc type early carcinoma of the rectum is reported. A 62-year-old man, who had been checked by immunological latex agglutination faecal occult blood testing, underwent a colorectal examination at Hakodate Chu-o Hospital. A barium enema revealed a slightly elevated lesion with a central depression in the lower rectum. Colonoscopic examination showed a IIa + IIc type of early rectal carcinoma. Study of the resected specimen also confirmed a IIa + IIc type early rectal carcinoma, 17 x 15 mm in diameter. Histologically, a lesion was located within the mucosa and consisted of both a carcinoma and an adenoma. Immunological latex agglutination faecal occult blood testing was thought to be useful for mass screening detection of a colorectal carcinoma.
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PMID:[A case of IIa + IIc type early carcinoma of the rectum, with no invasion of the submucosa]. 273 78

131 colorectal cancers, less than 3 cm in diameter, experienced at Juntendo University Hospital in Oct. 1977 through Dec. 1988 were studied with respect to their radiological and macroscopic features. Macroscopic features of the cancers were classified into type a (a lesion with a long stalk), type b (a subpedunculated or sessile lesion), type c (a plaque-like lesion) and type d (a lesion with a depression). Type a is early cancer. An early cancer of type b was mostly demonstrated as a lobular pattern of tumor surface, and an advanced cancer as a nodular pattern. Type c less than 1 cm in diameter was seen a sm cancer. A sm cancer of type d was mostly demonstrated as a faint barium fleck of the depression, an advanced cancer as a mild barium fleck. By deformed colonic wall in profile view, an early cancer was mostly demonstrated as a thorn shape deformity, sm or pm cancer as an arch shaped deformity and a cancer with deeper cancerous invasion than pm as a trapezoid deformity.
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PMID:[Radiological findings of cancerous invasion in colorectal cancer less than 3 cm in diameter]. 274 51

Zinc ions, which are unevenly distributed in the CNS and can be released from nerve terminals, have been implicated as causative agents in epileptogenesis. The present study has shown that intraventricular administration to anesthetized rats causes seizure activity of the ECOG and convulsions. Since the manner in which zinc influences neuronal activity and triggers convulsions is unclear, studies were also made of its effect on spontaneous and evoked activity in the rat forebrain. It was found that iontophoretic application of zinc to cortical neurons causes slow and often prolonged increases in firing rate, usually accompanied by bursts of high frequency discharge in just under half the studies. Another cation, barium, evoked excitatory responses of a similar type and a reduction in potassium permeability may underlie the effects of both cations. In contrast, calcium, magnesium, manganese and cerium caused short duration depressant effects. The depression induced by calcium, but not by the other cations, could be blocked by zinc. Similarly, in the hippocampus zinc depressed calcium-dependent potentiation in subfield CA3 evoked by paired-pulse stimulation of mossy fibers; excitatory effects (namely an increase in spike amplitude and appearance of multiple population spikes) were seen at higher zinc concentrations. The depressant effects of an enkephalin analog on cortical firing rate were also blocked by zinc, consistent with studies from another laboratory suggesting enkephalin/zinc interactions. In contrast, the depressant effect of GABA could not be blocked by zinc, although an antagonism has been reported in the lobster muscle. Firm conclusions regarding the mechanism(s) underlying the triggering of seizure activity by zinc cannot yet be drawn, but the results of these studies would be consistent with an interference with calcium and/or potassium ion activity rather than with GABA binding sites.
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PMID:Effect of zinc on neuronal activity in the rat forebrain. 302 63

Presented is the case of a patient, a 56-year-old female, who had complained of bloody stool and constipation. A barium enema and endoscopic examination revealed a tumor (Type 2) with a crater surrounded by a thick embankment, extending from the anterior wall to the left wall of the lower rectum. Biopsy specimens of the tumor disclosed a well-differentiated adenocarcinoma. A FT-207 suppository (1500 mg/day) was administered preoperatively for 50 days (total dose 75 g). On February 16, 1987, the patient underwent an abdominoperineal excision. The resected specimen took on the appearance of a chronic ulcer with an irregular depression, measuring 2.0 x 3.0 cm in size, in the lower rectum. The histology of the lesion also indicated a chronic ulcer, the base of which consisted of fibrosis covered with regenerative mucosa. No cancer cells or nests were demonstrated even serial tissue sections. As far as the rectal carcinoma is concerned, there has been no reported case of its disappearance by preoperative chemotherapy. The above results suggest that preoperative adjuvant chemotherapy can be quite effective against an advanced rectal carcinoma.
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PMID:[A case of rectal carcinoma that disappeared following preoperative chemotherapy with an FT-207 suppository--confirmed by a thorough histologic examination of the resected specimen]. 314 23

The effects of increasing rest periods on rest contractions and rest potentiation were analysed on isometric contractions of guinea pig papillary muscles at room temperature. Rest contraction amplitude is dependent on pause duration and potentiated for short pauses, which decreases as the rest period increases. their inotropic state is also dependent on the inotropic state of steady state control contractions. This statement is validated by the interdependence between control contractions and rest contractions amplitude and also because positive (5.0 mM CaCl2) and negative (0.5 mM NiCl2)inotropic interventions do not change the time course of dF/dt pause duration curves. They also show a slow activation characterized by a prolonged TTP that depends on pause duration being observed even in contractions occurring after short pauses. Rest contractions can be elicited under depolarized conditions produced by TKBa (Tyrode with high potassium and barium) and TKAdr (Tyrode with high potassium and adrenaline), showing that they are dependent on calcium influx occurring during the slow response of the cardiac action potential. The present study, carried out under depolarized conditions and in low extracellular Na+, shows that Na+ entry during the Na-dependent fast component of the action potential is necessary for the occurrence of rest potentiation. These findings suggest that the intracellular Na+, that can be exchanged by external calcium with the Na/Ca exchange mechanism, is necessary for the occurrence of the rest potentiation and to avoid the accelerated depression of the rest contractions with increasing pause duration.
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PMID:Mechanical behavior of rest contractions in cardiac muscle. 320 99

1. The action of acetylcholine (ACh) on the hyperpolarization-activated ('pacemaker') current if was studied in single myocytes from the sino-atrial (SA) node region of the rabbit heart, where low doses of ACh slow spontaneous activity by prolonging the diastolic depolarization phase. 2. Besides activating an outward component at voltages positive to the K+ equilibrium potential (iK,ACh), ACh depressed the current if activated on hyperpolarization at concentrations in the range 0.03-1 microM. 3. The ACh-dependent if depression was dissected from modifications of iK,ACh by blocking iK,ACh with barium and was studied under conditions that minimized the interference of other current changes caused by ACh. 4. The study of if modification by ACh with three-pulse protocols and the measurement of fully activated I-V relations of if with and without ACh revealed that ACh acted on if by shifting the current activation range to more negative voltages, with no obvious alteration of the fully activated current amplitude. 5. The action of ACh on if was opposite to that caused by catecholamines. The presence of isoprenaline (IP) did not prevent ACh inhibition of if, nor did the presence of ACh prevent the if stimulation caused by IP. The effects of IP and ACh on if were additive. 6. The ACh-induced inhibition of if was reversed by addition of atropine and could be mimicked by muscarine, indicating that muscarinic receptors mediate it. The implications of these findings on the regulation of pacemaker activity by ACh is discussed.
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PMID:Inhibition of the hyperpolarization-activated current (if) induced by acetylcholine in rabbit sino-atrial node myocytes. 325 98


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