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Biomedical subjects

S K Kulkarni

Publications and source records attributed to S K Kulkarni.

At least 217 records · Page 12Linked to original sources

Alpha 2 adrenoceptor-mediated contraction of frog rectus abdominis muscle.

Effect of various concentrations of clonidine (1.875 X 10(-11) to 1.875 X 10(-6) M) was investigated on rectus abdominis muscle of frog. In lower concentrations it neither had any effect per se nor did it alter the contractile effect of acetylcholine. However, a higher concentration of clonidine (1.875 X 10(-6) M) evoked characteristic slow but sustained contractions. Such an effect was not observed with epinephrine, norepinephrine or isoprenaline. Clonidine-induced sustained contractions were resistant to d-tubocurarine (2.545 X 10(-9) M) but susceptible to blockade by yohimbine (5.116 X 10(-8) M), an alpha 2 antagonist, and verapamil (2.04 X 10(-8) M), a calcium channel blocker. Probably activation of post-synaptic alpha 2 adrenoceptors by clonidine was responsible for the observed effect. This is further supported by the observation that guanfacine, a more specific alpha 2 adrenoceptor agonist, also evoked identical, slow and sustained contractions which could be readily reversed by yohimbine.

Abdominal Muscles↗

Facilitation of diazepam action by anticonvulsant agents against picrotoxin induced convulsions.

A subeffective dose (2 mg/kg) of diazepam produced only 50% protection against picrotoxin-induced (PTX) convulsions in rats. Simultaneous administration of GABA and other GABA-ergic substances such as piracetam and sidium valproate, which did not have any effect by themselves, potentiated diazepam action. The onset of convulsions and mortality due to PTX were significantly delayed. The other conventional anticonvulsants phenobarbitone, phenytoin and ethosuximide also enhanced the protective effect of diazepam. Inosine, a putative benzodiazepine ligand, also enhanced diazepam action. These observations are explained on the basis of data from in vitro studies indicating that GABA-ergic agents and barbiturates enhance both the number of benzodiazepine binding sites and benzodiazepine binding. The protective effect of clonidine, however, may be mediated by a different mechanism unrelated to the GABA-ergic system.

Animals↗

Possible mechanism of digoxin-induced convulsions.

Intraventricular (IVT) administration of digoxin (7.5 micrograms) induced 'popcorn-type' convulsions in rats. Though the convulsions looked similar to morphine-induced seizures, naloxone failed to antagonize these effects. Other anticonvulsants like phenobarbitone, ethosuximide, or GABAergic substances like piracetam and semicarbazide also had no protective effect against digoxin-induced convulsions. While calcium chloride potentiated these effects of digoxin, phenytoin, magnesium chloride, and potassium chloride treatment showed blocking actions. These observations suggest the involvement of Na/K-ATPase system in digoxin-induced convulsions. Clonidine and diazepam also provided protection against digoxin-induced convulsions through an unknown mechanism.

Animals↗

Effect of purinergic substances on rectal temperature in mice: involvement of P1-purinoceptors.

Effect of adenosine, 2-chloroadenosine (P1-purinoceptor agonists) and adenosine triphosphate (ATP), adenosine-5'-tetraphosphate (P2-purinoceptor agonists) on body temperature was studied in mice. Adenosine (7.5-200 mg/kg) as well as 2-chloroadenosine (0.25-7.5 mg/kg) induced hypothermia in a dose-dependent manner. However, ATP or adenosine-5'-tetraphosphate did not show any effect on body temperature. Caffeine and theophylline, P1-purinoceptor antagonists, blocked the hypothermic response of adenosine and 2-chloroadenosine. Treatment with quinidine or phenoxybenzamine (non-specific P2-purinoceptor antagonists) did not modify the hypothermic response. Similarly, treatment with drugs which modify adrenergic (reserpine, propranolol, labetalol or haloperidol), serotonergic (cyproheptadine) or histaminergic functions failed to block adenosine or 2-chloroadenosine-induced hypothermia. These results demonstrated that P1-purinoceptors mediated the hypothermic response of these purines.

2-Chloroadenosine↗

Evidence for the presence of P1- and P2-purinoceptors in rat caecum.

Adenosine, 2-chloroadenosine, adenosine triphosphate (ATP) and adenosine tetraphosphate induced concentration-dependent relaxation of rat caecum. Caffeine as well as theophylline, at concentrations (25-100 microM) lower than that known to produce significant phosphodiesterase inhibition, shifted the concentration-response curve for adenosine to the right in a parallel fashion without diminishing the maximal response. The pA2 values for caffeine and theophylline against adenosine were found to be 4.6 +/- 0.26 (slope = 0.97 +/- 0.05) and 4.9 +/- 0.28 (slope = 0.98 +/- 0.07), respectively. Though the relaxant effect of adenosine tetraphosphate was blocked in a non-competitive manner by quinidine (5 microM) and phenoxybenzamine (25 microM), theophylline or caffeine (50 microM) failed to block this response. Similarly, quinidine also blocked the relaxant effect of ATP in a non-competitive manner. Besides, the relaxant effect due to adensine was rapid in onset as compared to a slow relaxant effect of ATP. These observations suggest the presence of P1- and P2-purinoceptors in the caecum. The activation of these receptors by adenosine and ATP, respectively, leads to relaxation of the tissue.

2-Chloroadenosine↗

Reversal by serotonergic agents of reserpine-induced hyperalgesia in rats.

Reserpine (4 mg/kg) induced a time-dependent reduction in pain threshold (hyperalgesia) as observed by the tail-flick technique in rats. Serotonin, its precursor 5-hydroxytryptophan or the receptor agonist, quipazine reversed the reserpine-induced hyperalgesia. On the other hand, piribedil, amantadine, imipramine or desipramine treatment failed to reverse the reserpine-induced hyperalgesia. Similarly, intracerebroventricular administration of dopamine or noradrenaline also had no effect on reserpine-induced hyperalgesia. These observations not only suggested a role of serotonin in hyperalgesia but also that reserpine hyperalgesia is suitable for selective study of serotonin-mediated responses in rats.

5-Hydroxytryptophan↗

Actions of clonidine on convulsions and behaviour.

Pretreatment of rats and mice with clonidine (0.5-5 mg/kg, intraperitoneally) protected the animals against tonic convulsions induced by picrotoxin, strychnine and maximal electroshock, respectively. The time of onset of convulsions as well as mortality due to picrotoxin and strychnine were delayed in the clonidine pretreated groups as compared to controls. Clonidine (1 mg/kg) blocked the extensor phase of the electroshock convulsion. In reserpinized animals the severity of electroshock-induced seizures was reduced by clonidine pretreatment. Clonidine also caused an increase in the food consumption behaviour in mice subjected to novel situation and food. Its effects were comparable to diazepam, an antianxiety agent. In another experiment, clonidine (0.5-5 mg/kg) counteracted the perphenazine-induced catatonia in rats. It is possible that the observed anticatatonic effect of clonidine may be due to its presynaptic activity, but the actual mechanism of this action is not yet understood.

Animals↗

Modification of drug-induced catatonia and tremors by quapazine in rats and mice.

Administration of perphenazine, tremorine, nicotine and harmine induced Parkinson-like symptoms in rats and mice. The efficacy of quipazine, a serotonin agonist, in antagonizing these drug-induced Parkinsonian symptoms was assessed. Combinations of this drug with other antiparkinsonian agents such as scopolamine, diphenhydramine and amantadine were also studied in the manifestation of Parkinson-like symptoms in the animal models. The results indicate that quipazine, a central serotonergic agent, counteracted some of the drug-induced symptoms of pseudoparkinsonism in laboratory animals. Cholinergic, dopaminergic and histaminergic receptors play an important role in the manifestations of these symptoms.

Animals↗

Modification by levo-propranolol of tremors induced by harmine in mice.

It has been recently reported that the levo isomer of propranolol possesses anti-serotonin properties in animals. Since harmine-induced behavioural changes in mice are reported to be mediated through central serotonergic receptors, an attempt was made to test whether 1-propranolol would also modify harmine-induced responses by virtue of its anti-serotonergic or anti-adrenergic property. The results indicated that l- and dl-propranolol inhibited central serotonin receptor mediated responses to harmine in mice, a finding that is analogous to other recent observations.

Animals↗

New drug metabolism inhibitor of marine origin.

Dactylyne, an acetylenic dibromochloro ether, was isolated from the sea hare Aplysia dactylomela and characterized pharmacologically. It had no direct effect on the cardiovascular, respiratory, and central nervous systems of mice, rats, and guinea pigs. However, a 25-mg/kg ip dose of dactylyne prolonged pentobarbital sleep time in mice by more than 10 hr. This potentiation was subsequently determined to be due to the inhibition of pentobarbital metabolism by dactylyne since the elimination half-life of pentobarbital in the dactylyne-treated mice increased several folds. Dactylyne was nontoxic up to 200 mg/kg iv. The unique structure, high potency, and relatively nontoxic nature of dactylyne make it an interesting pharmacological substance of marine origin.

Animals↗