ABSTRACT
Glucotoxicity contributes to beta-cell dysfunction through oxidative stress. Our previous study demonstrated that tualang honey ameliorated renal oxidative stress and produced hypoglycemic effect in streptozotocin (STZ)-induced diabetic rats. This present study investigated the hypothesis that hypoglycemic effect of tualang honey might partly be due to protection of pancreas against oxidative stress. Diabetes was induced by a single dose of STZ (60 mg/kg; ip). Diabetic rats were randomly divided into two groups and administered distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). Similarly, two groups of non-diabetic rats received distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). The animals were treated orally for 28 days. At the end of the treatment period, the honey-treated diabetic rats had significantly (p<0.05) reduced blood glucose levels [8.8 (5.8)mmol/L; median (interquartile range)] compared with the diabetic control rats [17.9 (2.6)mmol/L]. The pancreas of diabetic control rats showed significantly increased levels of malondialdehyde (MDA) and up-regulation of superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Catalase (CAT) activity was significantly reduced while glutathione-S-transferase (GST) and glutathione reductase (GR) activities remained unchanged in the pancreas of diabetic rats. Tualang honey significantly (p<0.05) reduced elevated MDA levels. Honey treatment also restored SOD and CAT activities. These results suggest that hypoglycemic effect of tualang honey might be attributed to its antioxidative effect on the pancreas.
Subject(s)
Antioxidants/pharmacology , Diabetes Mellitus, Experimental/prevention & control , Honey , Pancreas/drug effects , Animals , Antioxidants/analysis , Blood Glucose/drug effects , Catalase/analysis , Catalase/metabolism , Glutathione Peroxidase/metabolism , Glutathione Reductase/analysis , Glutathione Reductase/metabolism , Glutathione Transferase/analysis , Glutathione Transferase/metabolism , Lipid Peroxidation/drug effects , Male , Malondialdehyde/metabolism , Pancreas/enzymology , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/analysis , Superoxide Dismutase/metabolism , Up-Regulation/drug effectsABSTRACT
Construction of a genetic linkage map is necessary to apply marker-assisted selection tools in a crop improvement program. Except for the recent studies from two laboratories, most of the previous studies have shown little or no DNA polymorphism in cultivated groundnut (Arachis hypogaea L.). In the present study, 70 selected genotypes, representing variability for several morphological, physiological, and other characters, were studied for polymorphism employing random amplified polymorphic DNA (RAPD) assay with 48 oligonucleotide primers. Of the 48 oligonucleotide primers only 7 (14.6%) yielded polymorphic amplification products. The total number of bands from the 7 primers was 408, of which 27 were polymorphic. Detection of polymorphism in cultivated groundnut opens up the possibility of development of its molecular map by judicious selection of genotypes that show DNA polymorphism. This approach will be useful for developing marker-assisted selection tools for genetic enhancement of groundnut for desirable traits.
Subject(s)
Genes, Plant , Nuts/genetics , Polymorphism, Genetic , Random Amplified Polymorphic DNA Technique/methods , Genetic Linkage , Genetic Markers , GenotypeABSTRACT
The baroreflex-induced changes in heart rate in chloralose anaesthetized and artificially ventilated cats (2.5-4.0 kg) before and after pretreatment with calcium channel blockers (CCBs) were compared. Baroreflex mediated changes in heart rate (HR) were elicited by raising and lowering the systemic blood pressure with intravenous injections of phenylephrine and sodium nitroprusside, respectively. The effects of three CCBs, verapamil, diltiazem and nifedipine administered either intravenously (i.v.) or intracisternally (i.c.) were studied. Verapamil administration markedly inhibited the reflex bradycardia as well as the tachycardia following either i.v. or i.c. administration. Intracisternally, a relatively smaller dose of verapamil produced an effect comparable in magnitude and duration, to a higher i.v. dose. The reflex bradycardia was inhibited following i.v., but not i.c. administration of nifedipine while the reflex tachycardia was not affected significantly by either i.v. or i.c. nifedipine. Intravenous diltiazem did not appear to affect the reflex bradycardia or tachycardia significantly. It is suggested that verapamil administration interacts with central cardiovascular integrating mechanisms to reduce the gain of the baroreflex function. Nifedipine and diltiazem are relatively free from this effect.
Subject(s)
Calcium Channel Blockers/pharmacology , Pressoreceptors/drug effects , Reflex/drug effects , Animals , Blood Pressure/drug effects , Cats , Female , Heart Rate/drug effects , Male , Nitroprusside/pharmacology , Phenylephrine/pharmacology , Pressoreceptors/physiologyABSTRACT
2-Mercapto-5-[4'-methoxy phenyl thiourea]-1,3,4-thiadiazole (2a-c) prepared by the condensation of 2-amino-5-mercapto-1,3,4-thiadiazole (1) with substituted phenyl isothiocyanates. Further on cyclisation with malonic acid in the presence of acetyl chloride gave the corresponding 2-mercapto-5-[3-(4-methoxy phenyl)-2-thioxo-2-5-dihydro-4, 6-pyrimidionoyl]-1,3,4-thiadiazole (3a-c) [sequence: see text]. This on further reaction with substituted aryl aldehydes in presence of zinc chloride gave 2-mercapto-5-[3-(4'-methoxy phenyl)-2'-thioxo-2',5'-dihydro-4',6' -pyrimidionoyl 5'-phenyl carboxaldehyde]-1,3,4- thiadiazole (4a-g) [sequence: see text]. The compounds were screened for antidepressant activity and compared with antidepressant (imipramine).
Subject(s)
Antidepressive Agents/chemical synthesis , Pyrimidines/chemical synthesis , Thiazoles/chemical synthesis , Animals , Antidepressive Agents/pharmacology , Behavior, Animal/drug effects , Female , Male , Mice , Pyrimidines/pharmacology , Thiazoles/pharmacologyABSTRACT
The effects of intravenous administration of verapamil, nifedipine and diltiazem on sympathetic stimulation-induced increase in heart rate (HR) and blood pressure (BP) have been investigated in chloralose-anaesthetized and artificially-ventilated cats. Verapamil (300 micrograms kg(-1) i.v.) produced a significant inhibition of sympathetically-induced tachycardia and pressor responses. The same dose of verapamil did not significantly alter adrenaline (2 micrograms kg(-1) i.v.) induced increase in HR and BP. In contrast, neither the sympathetically-induced nor the adrenaline-induced pressor and tachycardiac responses were significantly affected by nifedipine or diltiazem. These results demonstrate that peripherally administered verapamil but not nifedipine and diltiazem can inhibit cardiovascular sympathetic neurotransmission and this can possibly contribute to its effects on HR and BP.
Subject(s)
Blood Pressure/drug effects , Heart/innervation , Synaptic Transmission/drug effects , Tachycardia/chemically induced , Verapamil/pharmacology , Animals , Cats , Diltiazem/pharmacology , Epinephrine/pharmacology , Female , Heart/drug effects , Heart Rate/drug effects , Injections, Intravenous , Male , Nifedipine/pharmacologyABSTRACT
In the present study, an attempt has been made to elucidate the role of alpha 2-adrenoceptors in reserpine-induced emesis in pigeons. Reserpine was found to induce dose-dependent emesis and a 500 micrograms kg-1 dose was found to be the 100% emetic dose. alpha 2-adrenoceptor agonists clonidine and alpha-methylnoradrenaline inhibited the reserpine induced emesis. Out of the two selective alpha 2-adrenoceptor antagonists idazoxan and yohimbine, only the latter induced a dose-dependent emesis. However, both the drugs potentiated reserpine-induced emesis and antagonised its inhibition by clonidine. Prior depletion of monoamines by reserpine also blocked the emetic response of reserpine. These observations indicate that release of monoamines is responsible for its emetic response in pigeons which is modulated by presynaptic alpha 2-adrenoceptors in a predictable manner.
Subject(s)
Receptors, Adrenergic, alpha-2/physiology , Reserpine/pharmacology , Vomiting/chemically induced , Animals , Clonidine/pharmacology , Columbidae , Dioxanes/pharmacology , Female , Idazoxan , MaleABSTRACT
The aim of the present study was to investigate whether clonidine and morphine interact positively to produce analgesia against the low intensity tonic pain represented by the formalin model in rats. Sub-threshold doses of morphine (0.5 mg kg-1) and clonidine (0.025 mg kg-1) were found to elicit marked antinociceptive effects when co-administered intraperitoneally, 15 min prior to formalin challenge. Repeated administration of this combination for eight days did not exhibit any significant decay of this analgesic response, whilst morphine (2 mg kg-1)-induced analgesia, deteriorated after similar administration. Clonidine and morphine thus exhibit a supra-additive effect against low intensity pain with negligible potential for induction of tolerance. This finding may be relevant for the long term control of chronic pain in certain clinical conditions.
Subject(s)
Clonidine/therapeutic use , Morphine/therapeutic use , Pain/drug therapy , Animals , Dose-Response Relationship, Drug , Drug Synergism , Female , Formaldehyde , Injections, Intraperitoneal , Male , Pain/chemically induced , Pain Measurement/drug effects , Rats , Rats, WistarABSTRACT
Contractions of the cat nictitating membrane have been used to explore the effects of calcium channel blockers on neurotransmission in vivo, by comparing the effects of verapamil and nifedipine on contractions of nictitating membrane following either electrical stimulation of the superior cervical ganglion or intravenous injection of the alpha-adrenoceptor agonist phenylephrine. Verapamil (0.3, 0.6 and 1.2 mg/kg, iv) produced a dose related and reversible inhibition of stimulation induced contractions but did not affect phenylephrine responses of nictitating membrane. Intravenous nifedipine (10, 20 and 40 micrograms/kg) produced inconsistent effects on both stimulation- and phenylephrine-induced contractions of the nictitating membrane. Thus only verapamil appears to selectively affect noradrenergic neurotransmission in this model, possibly by altering the neurotransmitter release from the terminals innervating the nictitating membrane in the cat.
Subject(s)
Adrenergic Fibers/drug effects , Synaptic Transmission/drug effects , Verapamil/pharmacology , Adrenergic Fibers/physiology , Adrenergic alpha-Agonists/pharmacology , Animals , Cats , Electric Stimulation , Female , Ganglia, Sympathetic/drug effects , Ganglia, Sympathetic/physiology , Male , Muscle Contraction/drug effects , Nictitating Membrane/drug effects , Nictitating Membrane/innervation , Nifedipine/pharmacology , Phenoxybenzamine/pharmacology , Phenylephrine/pharmacologyABSTRACT
The presence of opioidergic activity after i.p. injection of N-methyl-4-phenyl tetrahydropyridine (MPTP) has been investigated in albino mice by studying analgesia and the Straub reaction. MPTP (6.25-25 mg kg-1) produced a dose-related analgesic response and Straub reaction. These effects of MPTP were effectively antagonized by prior naloxone treatment but remained unaffected after the MAO-B inhibitor deprenyl. MPTP thus possesses significant opioidergic activity and this, unlike its neurotoxic actions, does not appear to be dependent on oxidative conversion to MPP+ (1-methyl-4-phenyl pyridinium).
Subject(s)
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology , Analgesia , Isoenzymes/metabolism , Monoamine Oxidase/metabolism , Narcotics/pharmacology , Selegiline/pharmacology , Animals , Female , Male , Mice , Mice, Inbred Strains , Naloxone/pharmacology , Posture , Reference ValuesABSTRACT
The possibility of a central component in the cardiovascular effects of peripherally administered calcium channel blockers has been explored through a comparison of the effects observed after intravenous (i.v.) and intracisternal (i.c.) administration of verapamil and diltiazem in chloralose-anesthetized and artificially ventilated cats. Both agents produced relatively greater effects after i.c. than after i.v. administration. The bradycardiac effect following i.c. as well as i.v. administration was totally abolished by bilateral cervical vagotomy, and the hypotensive effect was attenuated by this procedure. The results strongly suggest the existence of a central component in the cardiovascular effects of both agents.
Subject(s)
Calcium Channel Blockers/pharmacology , Cardiovascular System/drug effects , Animals , Blood Pressure/drug effects , Cats , Diltiazem/pharmacology , Female , Heart Rate/drug effects , Male , Verapamil/pharmacologyABSTRACT
The cardiovascular responses to ketamine injected intracisternally were examined in chloralose anaesthetized cats. Blood pressure and heart rate were recorded at different time intervals after intracisternal injection of drug or saline vehicle. The low doses of ketamine (0.5 or 1.0 mg) elicited dose dependent increase in blood pressure and heart rate. In contrast the high dose of ketamine (4 mg), produced a fall in blood pressure and heart rate. The cardiovascular response elicited by the low dose was naloxone insensitive and completely blocked by haloperidol, but not by dopamine antagonist pimozide. The vasodepressor and bradycardiac effect of the 4 mg dose was naloxone antagonizable. These data show that excitatory cardiovascular effects of the low dose result from a naloxone resistant site while in high doses an inhibitory effect is elicited by action at naloxone sensitive opiate receptors.
Subject(s)
Hemodynamics/drug effects , Ketamine/pharmacology , Receptors, Opioid/drug effects , Animals , Blood Pressure/drug effects , Cats , Cisterna Magna , Dose-Response Relationship, Drug , Haloperidol/pharmacology , Heart Rate/drug effects , Injections , Naloxone/pharmacology , Phencyclidine/pharmacology , Pimozide/pharmacology , Receptors, sigmaABSTRACT
Opioid induced locomotor excitation in mice was studied. Both morphine and fentanyl increased spontaneous locomotor activity (SLA). Pentazocine produced a significant inhibition of SLA and also blocked the effects of subsequent morphine and fentanyl, thereby underscoring the importance of mu receptors for the opioid induced enhancement of SLA. Serotonergic receptor blockade with cyproheptadine or depletion with fenfluramine blocked, while uptake blockade with clomipramine potentiated the excitatory effect of fentanyl. Thus a mu receptor-serotonin link for the expression of opioid induced locomotor excitation becomes evident.
Subject(s)
Motor Activity/drug effects , Narcotics/metabolism , Receptors, Opioid/metabolism , Receptors, Serotonin/metabolism , Animals , Clomipramine/metabolism , Clomipramine/pharmacology , Cyproheptadine/metabolism , Cyproheptadine/pharmacology , Fenfluramine/metabolism , Fenfluramine/pharmacology , Fentanyl/metabolism , Fentanyl/pharmacology , Mice , Morphine/metabolism , Morphine/pharmacology , Narcotics/pharmacology , Pentazocine/metabolism , Pentazocine/pharmacology , Premedication , Receptors, Opioid, mu , Serotonin AntagonistsABSTRACT
Intravenous veratrine induced alterations in cardiovascular parameters in cats were used as a tool for assessing the influence of central alpha-adrenoceptors over reflex adjustments in the heart rate and blood pressure. Blockade of central alpha 2-adrenoceptors with idazoxan or yohimbine, inhibited, while their activation by clonidine, as also blockade of alpha 1-adrenoceptors, with prazosin, potentiated the veratrine induced bradycardia. The hypotensive effect was relatively unaltered by these treatments. Low doses of clonidine potentiated the veratrine-induced bradycardia. It appears that alpha 2-adrenoceptor mechanisms exert greater control over the reflex regulation of heart rate than over reflex control of blood pressure.
Subject(s)
Blood Pressure/drug effects , Heart Rate/drug effects , Receptors, Adrenergic, alpha/physiology , Veratrine/pharmacology , Animals , CatsABSTRACT
Although peripheral axotomy of dorsal root ganglion cells in mice, rats and cats has been reported to generate spontaneous activity in sensory nerves, we did not find evidence for such activity in the hamster. In vitro, intracellular recording from L6-S1 dorsal root ganglion cells up to 6 weeks after axotomy did not reveal any evidence for either increased membrane excitability or spontaneous activity. Also, in the sciatic nerve-sectioned hamsters, there was a total absence of the self-mutilatory behaviour which has been reported in other rodents. These results support the hypothesis that species specific factors are important for the development of ongoing activity in sensory nerves following injury.
Subject(s)
Axons/physiology , Ganglia, Spinal/physiology , Neurons, Afferent/physiology , Animals , Cricetinae , ElectrophysiologyABSTRACT
Intrathecal injection of graded doses of angiotensin elicited a significant, dose-related rise in blood pressure without affecting heart rate. Tachyphylaxis appeared with repeated intrathecal injections but intravenous angiotensin could elicit pressor effects at this stage. Intrathecal administration of saralasin per se, did not affect resting heart rate or blood pressure. However, pretreatment with saralasin completely antagonized the intrathecal angiotensin-induced rise in blood pressure without significantly altering the effect of intravenous angiotensin. A facilitatory role for blood pressure regulation is suggested for the angiotensin receptors at the spinal cardiovascular loci.
Subject(s)
Angiotensin II/pharmacology , Blood Pressure/drug effects , Cardiovascular Physiological Phenomena , Receptors, Angiotensin/physiology , Spinal Cord/physiology , Animals , Cardiovascular System/drug effects , Dogs , Female , Heart Rate/drug effects , Injections, Spinal , Male , Receptors, Angiotensin/drug effects , Spinal Cord/drug effects , Subarachnoid SpaceABSTRACT
1. The active and passive membrane properties of neurons in the lower lumbar (L6, L7) or sacral (S1) dorsal root ganglia from golden hamsters were examined in vitro by means of conventional intracellular recording techniques. Data were collected from neurons exhibiting action potentials (AP) of 70 mV or more in amplitude. 2. Cells with axonal conduction velocities (CV) greater than 20 m/s were termed fast-A-cells, those with CVs between 2.5 and 20 m/s were termed A-delta-cells, and those with CVs less than 1 m/s were termed C-cells. 3. Fast-A-cells usually exhibited short-duration APs (2.51 +/- 0.41 ms, n = 19) followed by short (less than 50 ms) afterhyperpolarizations (AHPs). C-cells usually exhibited long-duration APs (10.5 +/- 0.69 ms, n = 18) followed by long-duration AHPs (much greater than 50 ms). The characteristics of APs in A-delta-cells (AP mean duration 3.34 +/- 0.42 ms, n = 32) were intermediate between those of fast-A- and C-cells. Long AHPs (duration much greater than 50 ms) were manifest in 43.8% of A-delta-cells. 4. A time-dependent sag in hyperpolarizing electrotonic potentials (rectification) was found in 68.8% of fast-A-cells, 45.5% of A-delta-cells, and 62.5% of C-cells. 5. To examine neuronal properties 1-6 wk after transection of the sciatic nerve (axotomy), cells were reclassified as SAP (short action potential) cells and LAP (long action potential) cells. Cells in the SAP category had AP durations less than 5 ms and included all fast-A-cells and the majority of A-delta-cells. The LAP category included cells with AP durations greater than 8 ms contained only C-cells. 6. Axotomy failed to decrease the CV of LAP cells or A-delta-cells in the SAP group. The CV of LAP cells may have increased (P less than 0.05), whereas that of SAP cells was unchanged. 7. The duration of the AP and AHP of SAP cells were slightly increased (0.1 greater than P greater than 0.05), whereas AP and AHP duration of LAP cells were unchanged after axotomy. AHP amplitudes of all cell types tended to be smaller (0.1 greater than P greater than 0.05). Axotomy did not alter the resting membrane potential or reduce the incidence of rectification in any cell type. 8. Invasion of the soma by axonally evoked APs was impeded in all cell types after axotomy even though a decrease (P less than 0.05) in rheobase of SAP cells occurred.(ABSTRACT TRUNCATED AT 400 WORDS)
Subject(s)
Axons/physiology , Ganglia, Spinal/physiology , Action Potentials , Animals , Cricetinae , Electrophysiology , Ganglia, Spinal/cytology , Ganglia, Spinal/ultrastructure , Mesocricetus , Neural Conduction , Neurons, Afferent/classification , Neurons, Afferent/physiology , Neurons, Afferent/ultrastructure , Reaction TimeABSTRACT
Axotomy produced an increase in the spike width and a decrease in amplitude of the afterhyperpolarization which followed the action potential in C-cells of bullfrog sympathetic ganglia. Although no change in B-cell conduction velocity was noted, C-cell conduction velocity increased significantly and approached that of B-cells. This change may reflect a process of dedifferentiation prior to the initiation of regrowth following axotomy.
Subject(s)
Ganglia, Sympathetic/physiopathology , Neural Conduction , Sympathetic Nervous System/injuries , Action Potentials , Animals , Axons/physiology , Nerve Fibers/physiology , Nerve Regeneration , Rana catesbeianaABSTRACT
Cholinergic receptors present in three medullary nuclei namely, the nucleus tractus solitarii (NTS), nucleus ambiguous (AMB) and the dorsal motor nucleus of the vagus nerve (DMV) have been studied with regard to their role in regulation of heart rate (HR), blood pressure (BP) and baroreceptor reflex activation induced bradycardia in cats. Microinjection of carbachol into NTS was without effect while administration of carbachol or pilocarpine into AMB and DMV elicited dose related decrease in HR without affecting BP. These effects were completely antagonized by ethylbenztropine. Bilateral muscarinic cholinoceptor blockade of either AMB or DMV, with ethylbenztropine, produced a partial inhibition of the baroreflex bradycardia while intracisternal ethylbenztropine completely abolished this reflex response. Involvement of muscarinic cholinoceptors of AMB or DMV in baroreflex mediated adjustments of HR is therefore suggested.
Subject(s)
Heart Rate , Medulla Oblongata/physiology , Pressoreceptors/physiology , Receptors, Muscarinic/physiology , Animals , Blood Pressure/drug effects , Carbachol/antagonists & inhibitors , Carbachol/pharmacology , Cats , Clonidine/pharmacology , Female , Heart Rate/drug effects , Male , Microinjections , Pilocarpine/antagonists & inhibitors , Pilocarpine/pharmacology , Pressoreceptors/drug effects , Receptors, Muscarinic/drug effects , Tropanes/pharmacologyABSTRACT
Microinjection of noradrenaline and clonidine into lateral medullary pressor area (LMPA) of chloralose anaesthetized cats produced dose dependent decrease in blood pressure without affecting heart rate, while phenylephrine did not elicit any cardiovascular response. Selective alpha 2-adrenoceptor antagonists idazoxan and piperoxan, microinjected locally, blocked the effects of the agonists but prazosin and phenoxybenzamine, which are relatively selective for alpha 1-adrenoceptors, failed to do so. Clonidine did not elicit any response in guanethidine pretreated cats but noradrenaline microinjected into LMPA of these animals induced a pressor response which was blocked by prazosin pretreatment. It is concluded that catecholaminergic fibres impinging upon this area inhibit the activity of the inhibitory second order baroreceptor neurone by activating alpha 1-adrenoceptors while alpha 2-adrenoceptors situated presynaptically on these inhibitory catecholaminergic nerve terminals are responsible for the manifestation of the hypotensive effect of clonidine and exogenously administered noradrenaline.