Biomedical subjects

J T Cheng

Publications and source records attributed to J T Cheng.

At least 145 records · Page 8Linked to original sources

PubMed1995

Stimulatory effect of dopamine on acid secretion from the isolated rat stomach.

The effect of dopamine (DA) on acid secretion was studied using the everted preparation of isolated rat stomachs. DA concentrations, measured by HPLC-ECD in the rumen, corpus and antrum were 1.06 nmol/mg protein, 0.49 nmol/mg protein and 2.92 nmol/mg protein, respectively. DA stimulated acid secretion at a concentration of 10 nM and elicited the maximum response at 10 microM, which was at a level approximately 1.56-fold that of the spontaneous secretion but only about half that of secretion induced by histamine at a concentration of 0.3 mM. The concentration-dependent stimulation by DA was antagonized by octopamine and SCH 23390. Failure of proglumide and cimetidine to affect this stimulation ruled out the participation of histamine and/or gastrin. Scopolamine and tetrodotoxin completely inhibited the acid secretion induced by low concentrations of DA but inhibited only partially the response induced by high concentrations of DA. The results obtained indicate that DA induces acid secretion via activation of the dopamine D1 receptor, located on the cholinergic neurons and on some nonneuronal cells, in the rat stomach.

Animals↗

PubMed1995

Antihypertensive effect of corilagin in the rat.

The antihypertensive effect of corilagin, one of the ellagitannins purified from the seeds of Euphoria longana Lam. (Sapindaceae), was investigated in the spontaneously hypertensive rat (SHR). Administration of corilagin into conscious SHR at 5 mg/kg produced an antihypertensive effect equivalent to that induced by 1 mg/kg of guanethidine. This dose-dependent hypotensive effect was comparable with that observed in anesthetized SHR animals. Corilagin did not modify the baroreflex sensitivity in phenylephrine-challenged SHR. Corilagin reduced plasma noradrenaline in a dose-dependent fashion, an effect that was maintained in adrenalectomized rats. Failure of the antagonists for alpha2-adrenoceptors, idazoxan and yohimbine, as well as for dopamine receptors, haloperidol and domperidone, to reverse the antihypertensive actions of corilagin ruled out the participation of these receptors. Moreover, corilagin attenuated the pressor effects of methoxamine and Bay K8644 to a similar degree, indicating the direct effect of corilagin on vascular activity in rats. These results suggest that corilagin possesses the ability to lower blood pressure through the reduction of noradrenaline release and (or) direct vasorelaxation.

Adrenergic alpha-Antagonists↗

PubMed1995

Effects of pregnancy and progesterone on autonomic function in the rat urinary bladder.

Previous studies have shown that pregnancy is associated with a decrease in cholinergic function in the rabbit urinary bladder. The present study aimed at evaluating the effects of pregnancy on the autonomic function of the rat urinary bladder and to elucidate whether progesterone is responsible for such alterations. Female Wistar rats, 3 months old, were divided into four groups: (1) 2-week pregnant rats; (2) rats given daily intramuscular injections of progesterone 5 mg/kg for 2 weeks; (3) rats given intramuscular injections of vehicle for 2 weeks, and (4) controls. Cystometry showed a significant increase in bladder capacity in the pregnant rats. The wet weight of the pregnant rat bladder was also significantly increased. Histologic study revealed increased bladder wall thickness with interstitial edema and urothelium proliferative changes to a papillary configuration in these pregnant bladders. Bladder muscle strip study showed significantly reduced maximum contractile responses to acetylcholine and methoxamine in the pregnant and the progesterone groups. Muscarinic receptor binding study demonstrated reduced Bmax in the pregnant rats and rats receiving progesterone injections (control group Bmax = 57 +/- 11, pregnant group Bmax = 44 +/- 8, p < 0.05; progesterone group Bmax = 40 +/- 7, vehicle group Bmax = 58 +/- 9 fmol/mg protein, p < 0.05). The contractile response to lower concentrations (10(-6) mol/l to 10(-4) mol/l) of ATP was elevated in the pregnant rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Effect of alpha-chymotrypsin on the nonadrenergic, noncholinergic contraction of the rat urinary bladder in vitro.

The role of peptides in mediating the nonadrenergic, noncholinergic (NANC) response of the rat urinary bladder was studied. Electrical stimulation of muscle strips from 3-month-old female Wistar rat urinary bladders in the presence of autonomic blockers (atropine 10(-6) mol/l, propanolol 10(-6) mol/l, phentolamine 10(-6) mol/l, and guanethidine 10(-6) mol/l) showed NANC contraction accounting for 60% of the maximum contractile responses at 40 Hz. Frequency-response studies showed that in the presence of alpha-chymotrypsin (2 U/ml, 30-min incubation), the NANC contractile responses to electrical stimulation at lower frequencies (3-10 Hz) were enhanced (p < 0.05; n = 9). However, no significant differences were observed at higher frequencies (20-40 Hz). With repetitive 4-Hz stimulation, alpha chymotrypsin caused a 19% increase in the NANC contractile response (p < 0.05; n = 8). It is postulated that the NANC response of the rat bladder smooth muscle is composed of an excitatory (contractile) and an inhibitory (relaxant) component. Some peptide(s) is/are responsible for mediating the inhibitory response.

Acetylcholine↗

PubMed1995

Role of cyclic adenosine monophosphate in prostaglandin E1-induced penile erection in rabbits.

To investigate the role of cyclic adenosine monophosphate (cAMP) in penile erection in relation to the effect of prostaglandin E1 (PGE1) male adult New Zealand white rabbits were utilized as a model to study intracavernous pressure (ICP) in vivo. After intracavernous injection of PGE1 (0.2-1.6 micrograms/kg) and 8-bromocyclic adenosine monophosphate (8-Br-cAMP, 0.5-1.5 mg/kg), both drugs raised the ICP in a dose-dependent manner. The increased ICPs induced by PGE1 and 8-Br-cAMP were 33.4 +/- 8.12 and 24.1 +/- 4.9 mm Hg, respectively (p < 0.05, paired Student's t test). Administrations of cyclic adenosine monophosphothioate, Rp-isomer (cAMP antagonist, 0.02-0.08 mumol/kg) prior to PGE1 injections inhibited the effect of PGE1 in vivo in a dose-dependent manner. The systemic blood pressures and heart rates in rabbits were unchanged during all the intracavernous injections. The corpus cavernosal tissues isolated from rabbits were studied for the cAMP contents after incubation of different doses of PGE1 in vitro. The cAMP contents were also elevated in a manner parallel with the increases in PGE1 concentrations (3-9 microM). We conclude: (1) the feasibility of intracavernous injection of vasoactive drugs is similar to that in man, thus the rabbit can be used as a suitable alternative for the studies of penile erection, and (2) cAMP is mediated in PGE1-induced relaxation of the rabbit corpus cavernosum, and the cAMP system only participates partially in penile erection.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1995

Prophylactic effects of sucralfate and geraniin on ethanol-induced gastric mucosal damage in rats.

The aim is to study the protective effects of topical sucralfate and geraniin on acidified ethanol (EtOH dissolved in 100 mM HCI plus 54 mM NaCl)-induced gastric acid back-diffusion, mucus production and mucosal ulcerations in the rat. After irrigation the stomach with acidified EtOH (10-40% v/v) for 3 hrs, a concentration-dependent increase in acid back-diffusion and in mucosal lesions, and -dependent reduction in mucus production was found. These ulcerogenic effects of EtOH were dose-relatedly inhibited by pretreatment of intragastric sucralfate (10-200 mg/kg). A high correlation (r = -0.9572) between sucralfate-induced inhibition in acid back-diffusion and -induced reduction in mucosal ulceration provoked by 30% EtOH was observed. Geraniin (10-100 mg/kg), given 30 min prior to EtOH perfusion, produced potent inhibitory effects on those ulcerogenic parameters provoked by EtOH in a dose-dependent manner. The correlation (r = -0.8638) between geraniin-induced inhibitions in acid back-diffusion and in mucosal ulceration produced by EtOH was achieved. These cytoprotective effects of sucralfate and geraniin were further confirmed by morphological and histological studies. The results suggested that the protective effects of sucralfate and geraniin on gastric mucosa against acidified EtOH-induced damage are at least partly through the inhibition in acid back-diffusion and the elevation of gastric mucus production.

Animals↗

PubMed1994

Inhibitory effect of neuropeptide Y (NPY) on the in vitro activity of tyrosine hydroxylase.

Neuropeptide Y (NPY) is found to be costored with norepinephrine (NE) in vesicles of the nerve terminals. Tyrosine hydroxylase (TH), the synthetic enzyme of NE, has been mentioned to be a rate-limiting step. In an attempt to understand the effect of NPY on TH activities, an in vitro assay is carried out using chromatographic analysis of 3,4-dihydroxyphenylalanine (DOPA) formation from tyrosine. NPY (40-120 pmol/ml) produced a dose-dependent depression of DOPA formation catalysed by the adrenal TH of rats. Lineweaver-Burk plot (Km = 156 microM, Vmax = 1.05 nmol/h/mg protein) showed a non-competitive inhibition in NPY (80 pmol/ml, IC50)-treated samples. Moreover, failure of denatured NPY even at maximum concentration to influence the TH activities suggested the essential of nature form for NPY. Participation of pterine cofactor seems also negligible, because increase of 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine did not overcome the effect of NPY. These results indicate that NPY has the ability to inhibit the catalytic action of TH in the adrenal gland of rats.

Adrenal Glands↗

PubMed1994

Reticular thalamic inhibitory input to lateral hypothalamic neurons: a functional and histochemical determination.

Both the lateral hypothalamus (LH) and reticular thalamus (RT) have been implicated in the integration of a variety of vital functions. To determine relevant connections more specifically between cells of these two regions in the rat, functional neurophysiological and horseradish peroxidase (HRP) histochemical techniques were utilized. Single pulse electrical stimulation of the RT modified the discharge frequency of the majority of LH neurons tested. LH neuronal responses to RT stimulation included; inhibition (66.32%), excitation followed by inhibition (6.12%), and excitation (7.14%). Because RT stimulation resulted primarily in the inhibition of LH neuronal activity with a relative short mean latency of 1.87 +/- 0.23 ms, the existence of a possible direct inhibitory pathway from the RT to LH also was evaluated using HRP histochemistry. Retrogradely HPR labeled soma were identified in the RT after HRP was ejected extracellularly onto LH neurons, which exhibited a decrease in spontaneous activity in response to RT stimulation. These data demonstrate direct projections from the RT to the LH. In addition, HRP labeling of neurons and axons in the zona incerta-LH area following LH HRP ejections suggest this route as a synaptic pathway from RT to LH.

Action Potentials↗

PubMed1994

GABA inhibition of lateral hypothalamic neurons: role of reticular thalamic afferents.

GABA and reticular thalamic (RT) stimulation induced inhibition of lateral hypothalamic (LH) neuronal activity was studied to determine if RT inhibitory input to the LH is mediated by stimulation of GABA receptors. Seven barrel electrodes were utilized to record simultaneously from the LH during microiontophoretic application of GABA, glycine, bicuculline, picrotoxin, and electrical stimulation of the RT. GABA produced an ejection current-related decrease in LH neuronal activity that was antagonized, in a dose-related manner, by the simultaneous administration of picrotoxin or bicuculline. LH neurons were much less sensitive to glycine inhibition which also was relatively insensitive to the GABA receptor antagonists. RT electrical stimulation provided a short latency inhibitory input to LH neurons that was mimicked by the microiontophoretic administration of GABA. In addition, the microiontophoretic application of picrotoxin or bicuculline blocked the RT stimulation induced inhibition of LH neuronal activity. These data indicate that the inhibitory effects of both GABA and RT synaptic inputs onto LH neurons are mediated by stimulation of GABAA receptors and substantiates the involvement of GABA as the inhibitory transmitter of thalamic to hypothalamic projections.

Animals↗

PubMed1994

Antihypertensive activity of 6-O-galloyl-D-glucose, a phenolic glycoside from Sapium sebiferum.

The antihypertensive activity of a phenolic glycoside contained in the leaves of Sapium sebiferum was investigated. From intravenous screening using spontaneously hypertensive rats, 6-O-galloyl-D-glucose was identified as an active substance. The hypotensive action of this compound appears to be produced by an inhibition of noradrenaline release and/or a direct vasodilatation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1994

Influence of acetonylgeraniin, a hydrolyzable tannin from Euphoria longana, on orthostatic hypotension in a rat model.

Acetonylgeraniin, an active principle isolated from the seeds of Euphoria longana Lam. (Sapindaceae), reversed the fall in arterial blood pressure in conscious hypertensive rats (SHRs) with orthostatic hypotension induced by injection of hexamethonium into animals subjected to 90 degrees head-up tilts for 60 seconds. However, acetonylgeraniin failed to affect prazosin-induced orthostatic hypotension. Plasma noradrenaline (NA) and mean blood pressure were elevated dose-dependently by an intravenous injection of acetonyl-geraniin into the rats; this increase in blood pressure was totally abolished by prazosin. Failure of hexamethonium or pentolinium, the blockers of ganglionic nicotinic receptors, to influence the NA releasing action of acetonylgeraniin ruled out the participation of ganglionic stimulation. This NA-releasing action of acetonylgeraniin was, however, totally abolished by the inhibitors of noradrenergic nerve terminals, guanethidine or bretylium. Also, the activity of this tannin was not modified by adrenalectomy. Thus, a direct release of NA from the noradrenergic nerve terminals by acetonylgeraniin seems responsible for the reversing of orthostatic hypotension.

Animals↗

PubMed1994

Dopamine-induced inhibition of endogenous acetylcholine release from the isolated ileal synaptosomal preparations of guinea-pig mediated via alpha-adrenoceptors.

1. The effect of exogenous dopamine on the release of endogenous acetylcholine (ACh) from isolated ileal synaptosomal guinea-pig preparations was examined by means of high pressure liquid chromatography with electrochemical detection. 2. Release of ACh was induced by substance P or by depolarization with high potassium (50 mM) in a medium containing atropine propranolol and naloxone. 3. Dopamine produced a concentration-dependent inhibition of the evoked ACh release induced by substance P or in samples depolarized by high potassium. This action of dopamine was not reversed by the dopamine receptor antagonists either for the DA2 subtype domperidone, or for the DA1 subtype, SCH23390. Fenoldopam, the agonist of dopamine DA1 receptors, or quinpirole, the agonist of dopamine DA2 receptors, reduced the evoked ACh release, although only in high, non-dopamine-specific concentrations. 4. Failure of guanethidine or desipramine to inhibit this effect of dopamine ruled out mediation by endogenous noradrenaline. 5. Idazoxan and yohimbine reversed this dopamine-induced inhibition at concentration sufficient to abolish the action of clonidine. Influx of (45)Ca stimulated by substance P or high potassium into synaptosomal preparations was attenuated in the presence of dopamine. This inhibition by dopamine was also reversed by idazoxan or yohimbine but not by dopamine receptor antagonists. Moreover, the dopamine-induced inhibitions of both the ACh release and the influx of (45)Ca disappeared in the samples treated with pertussis toxin at a dose sufficient to abolish the action of clonidine. 6. It is concluded that dopamine suppresses the influx of calcium ions into cholinergic nerve terminals via an activation of alpha2-adrenoceptors coupled with a pertussis toxin-sensitive GTP-binding protein, resulting in the decrease of ACh release from ileal synaptosomes of guinea-pigs.

Acetylcholine↗

PubMed1994

Skimmianine and related furoquinolines function as antagonists of 5-hydroxytryptamine receptors in animals.

1. Skimmianine, kokusaginine and confusameline, three furoquinolines extracted from the leaves of Evodia merrillii (Rutaceae), were investigated to characterize their selective effects on subtypes of 5-hydroxytryptamine (5-HT) receptors. 2. In the isolated membranes of rat cerebrocortex, using [3H]-5-HT and [3H]-ketanserin as radioligands, skimmianine and the two other furoquinolines displaced radioligand bindings in a concentration-dependent manner. Lower concentrations were required to affect [3H]-ketanserin binding than [3H]-5-HT binding in the order skimmianine > kokusaginine > confusameline. 3. Furoquinolines inhibited 5-HT-induced contraction mediated by 5-HT2 receptors in the presence of methiothepin in rat isolated aorta. Also, the combination of furoquinolines with ketanserin showed an additive antagonism. 4. These furoquinolines were inactive on the 5-carboxamidotryptamine-induced relaxation of guinea-pig ileum, a 5-HT1-mediated event. However, 5-HT-induced contraction via 5-HT2 receptors was reduced by these furoquinolines in a way similar to that in blood vessels. 5. The failure of these compounds to affect the 5-HT-induced Bezold-Jarisch-like reflex in anaesthetized rats, the major 5-HT3-mediated action, ruled out an action on 5-HT3 receptors. 6. The results obtained suggest that three furoquinoline alkaloids may act on 5-HT receptors in animals, more selectively to the 5-HT2 subtype, in the order of skimmianine > kokusaginine > confusameline.

Animals↗

PubMed1994

Antihypertensive action of geraniin in rats.

The effects of geraniin, one of the ellagitannins purified from the leaves of Sapium sebiferum, on blood pressure were investigated in the spontaneously hypertensive rat (SHR). A single intravenous bolus injection of geraniin into anaesthetized SHRs lowered the arterial mean blood pressure in a dose-dependent manner without affecting the heart rate. A similar action was also observed in the normotensive (WKY) rat that received this compound at a higher dose. Geraniin did not modify the baroflex sensitivity in the phenylephrine-challenged SHR. This tannin reduced the plasma noradrenaline in a dose-dependent fashion which was not influenced by adrenalectomy. Failure of the antagonists, idazoxan and yohimbine for alpha 2-adrenoceptors as well as haloperidol and domperidone for dopamine receptors, to reverse the antihypertensive actions of geraniin ruled out the possible mediation of these receptors. Moreover, geraniin attenuated the pressor responses to exogenous noradrenaline and Bay K 8644 to a similar degree, indicating the direct effect of this compound on vascular activity in rats. These results suggest that geraniin possesses the ability to lower systemic blood pressure through the reduction of noradrenaline release or by direct vasorelaxation.

Adrenalectomy↗

PubMed1994

The effects of KB-2796 and BAY K 8644 on fentanyl-induced analgesia in rats.

We investigate the modulatory effects of subcutaneous administration of different doses of KB-2796 (1, 5 and 15 mg/kg), a new calcium channel blocker, and BAY K 8644 (0.25, 0.5 and 1 mg/kg), a calcium agonist, on fentanyl-induced analgesia (20 micrograms/kg) in rats. The drugs were tested individually as well as in combination with fentanyl. Dimethyl sulfoxide (DMSO) was used as a control. Nociceptive sensitivity was assessed by the tail-flick technique. When KB-2796 and BAY K 8644 were used alone, only KB-2796 at the dose of 15 mg/kg produced an effect that was significantly different from that of DMSO (p < 0.01). The effect was antinociceptive. When administered with fentanyl, KB-2796 at 5 and 15 mg/kg potentiated the analgesic effect of fentanyl (p < 0.05), but suppression of fentanyl analgesia by BAY K 8644 was not significant at any of the doses tested. Our data supports the hypothesis that the calcium ion is partially involved in fentanyl-induced analgesia.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1994

Betel quid chewing damaged gastric mucosa: protective effects of cimetidine and sodium bicarbonate.

The effects of cimetidine and NaHCO3 on gastric acid back-diffusion (either the H+ loss or the Na+, K+ and CA++ gain in the gastric lumen) and mucosal ulceration were studied in rats with chronic feeding of betel quid chewing (BQC)- or its individual component-containing food. After 30 and 90 days of feeding, the animal was fasted for 24 hrs and vagotomized. An acid solution (100 mM HCl plus 54 mM NaCl) with or without drugs was irrigated in the rat stomach for 3 hrs. The results indicated that BQC and its individual component produced a variety of change in enhancement in acid solution-induced acid back-diffusion and mucosal hemorrhagic ulceration but in decrease of gastric mucus secretion. These parameters were dose-dependently reversed by intragastric cimetidine (50-300 mg/kg) in BQC-treated rats. Similar but lesser effect than cimetidine (300 mg/kg) was obtained by intragastric administration of NaHCO3 (52 mg/kg). It is concluded that in BQC- or its component-feeding rats, the enhancement in acid back-diffusion and the reduction in mucus secretion are at least in part responsible for the formation of hemorrhagic ulceration which can be inhibited by intragastric cimetidine or NaHCO3.

Animals↗

PubMed1994

The effect of nifedipine on fentanyl-induced analgesia in rats.

We investigated the modulatory effect of subcutaneous administration of different doses of nifedipine (1.5 or 15 mg/kg), a calcium channel blocker, on fentanyl (15 micrograms/kg), an opioid mu-agonist, in rats. The drugs were tested individually as well as in combination. Normal saline and dimethyl sulfoxide were used as controls. Nociceptive sensitivity was assessed by tail-flick technique. No analgesic effect by nifedipine alone at any of the three doses was observed. A slight analgesic effect by fentanyl alone, lasting up to 60 minutes, was noted in the tail-flick responses only (p < 0.05). The combination of both drugs did not enhance or prolong the analgesic effect of fentanyl. The same results were obtained in a supplementary study using higher doses of fentanyl (30 micrograms/kg) with nifedipine (15 mg/kg). Our results suggested that, unlike other calcium channel blockers, nifedipine injected subcutaneously does not enhance fentanyl analgesia.

Analgesia↗

PubMed1994

Enhancement of antinociceptive effect of fentanyl by KB-2796 at spinal level.

Opioids inhibit the voltage-dependent calcium channel conductance, which is one of the mechanisms of opioid analgesia on the opioid receptor. According to the hypothesis that calcium antagonists can potentiate the analgesic effect of opioids, we designed a study to investigate the effects of KB-2796, a new calcium channel blocker, on the antinociception of fentanyl at the level of the spinal cord in rats. PE-10 catheters were chronically implanted in the lumbar intrathecal space of the rats. Tail-flick test was used to assess the nociceptive sensitivity. Fentanyl (1 microgram) and KB-2796 (50, 150 or 250 micrograms) were tested individually as well as in combination. Dimethyl sulfoxide (10%) was used as a control. All drugs were injected intrathecally. Fentanyl alone produced a significant but short duration (15-30 minutes) of antinociception. KB-2796 by itself did not show any antinociception at any of the doses tested. However, when KB-2796 at the higher doses (150 and 250 micrograms) was administered with fentanyl, the antinociceptive effect was significantly (P < 0.05) enhanced over that of fentanyl alone from 30 to 180 minutes after the injection. In conclusion, our results suggest that KB-2796 potentiates the analgesic effect of fentanyl at the spinal level. These data also support our hypothesis that calcium channel blockers may involve in the antinociception of opioids.

Analgesia↗