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R S Grewal

Publications and source records attributed to R S Grewal.

At least 19 recordsLinked to original sources
PubMed1998

The second messenger cAMP elicits eating by an anatomically specific action in the perifornical hypothalamus.

We have previously shown that a membrane-permeant analog of cAMP, 8-bromo-cAMP (8-br-cAMP), elicits a vigorous eating response when microinjected into the perifornical hypothalamus (PFH) or lateral hypothalamus (LH) of satiated rats, suggesting that increases in cAMP in these areas may be important in the neural control of eating. To determine the locus of this effect, we compared the ability of 8-br-cAMP (1-100 nmol/0.3 microl) to elicit eating after microinjection into the PFH, LH, or the following bracketing areas: the anterior and posterior LH, paraventricular nucleus of the hypothalamus, thalamus, and amygdala. 8-br-cAMP at 50 nmol elicited eating (>/=3.4 gm in 2 hr) exclusively in the PFH and LH. At 100 nmol, 8-br-cAMP elicited a larger response in these areas and elicited a smaller, more variable response in the thalamus. We similarly mapped the feeding-stimulatory effects of compounds that increase endogenous cellular cAMP in naive rats. Combined microinjection of matched doses (300 nmol) of 3-isobutyl-1-methylxanthine and 7-deacetyl-7-O-(N-methylpiperazino)-gamma-butyryl-forskolin was effective exclusively in the PFH, eliciting an average 2 hr food intake of 8.4 +/- 2.0 gm. Collectively, these results suggest that increases in cellular cAMP within a specific brain site, the PFH, may play a role in the neural stimulation of eating.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Stimulation of eating by the second messenger cAMP in the perifornical and lateral hypothalamus.

Despite intense study of neurotransmitters mediating hypothalamic controls of food intake, little is known about which second messengers are critical for these mechanisms. To determine whether adenosine 3',5'-cyclic monophosphate (cAMP) might participate in these mechanisms, we injected the membrane-permeant cAMP analog 8-bromo-cAMP (8-BrcAMP) hypothalamically in satiated rats. Injection of 8-BrcAMP (10-100 nmol) into the perifornical (PFH) and lateral hypothalamus (LH) dose dependently stimulated food intake of up to 15.7 g in 2 h. Significantly smaller responses were obtained with thalamic injections. In contrast to the strong stimulatory effects of PFH and LH 8-BrcAMP, cAMP and 8-bromo-guanosine 3',5'-cyclic monophosphate (100 nmol) were ineffective, suggesting a chemically specific, intracellular action. Consistent with this, combined PFH injection of 7-deacetyl-7-O-(N-methylpiperazino)-tau-butyryl-forskolin dihydrochloride and 3-isobutyl-1-methylxanthine, agents that increase endogeneous cAMP, stimulated eating of up to 9.9 g in 2 h. These results demonstrate that increases in PFH/LH cAMP can elicit complex, goal-oriented behavior, suggesting an important role for cAMP in hypothalamic mechanisms stimulating food intake.

1-Methyl-3-isobutylxanthine↗
PubMed1997

NMDA receptor coagonist glycine site: evidence for a role in lateral hypothalamic stimulation of feeding.

To investigate the role of the glycine coagonist binding site on the N-methyl-D-aspartate (NMDA) receptor in feeding control, we injected the glycine site antagonist 7-chlorokynurenic acid (7-CK) into the lateral hypothalamus (LH) of satiated rats before LH injection of NMDA, 7-CK (10-44 nmol) blocked the 6- to 10-g eating response elicited by NMDA. This block was reversed by LH pretreatment with glycine, arguing for a specific action at the glycine site. In contrast to the suppression produced by high doses, 7-CK at 0.1 nmol enhanced NMDA-elicited eating. For examination of behavioral specificity, 7-CK was injected into the LH before kainic acid (KA) or DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA). 7-CK at a dose of 0.1 nmol suppressed feeding elicited by KA or AMPA, but at 10 nmol it suppressed eating elicited by AMPA while enhancing eating elicited by KA. Finally, bilateral LH injection of 7-CK effectively suppressed eating produced by fasting. These findings support a role for the NMDA receptor coagonist glycine site in LH regulation of eating behavior.

Animals↗
PubMed1994

Immunomodulators in clinical practice.

Immunomodulators have opened new vistas in the management of the immunocompromised patient. They have been shown to enhance the efficacy of vaccines in infections, head and neck malignancy, the immunosuppressed and recently in AIDS. The mechanism of their action is discussed. They hold promise of further advances in immunotherapy.

Adjuvants, Immunologic↗
PubMed1985

Pharmacological profile of 1-methylsulphonyl-3-(1-methyl-5-nitro-2-imidazolyl)-2-imidazolidinone (Go-10213), a new antiprotozoal agent, in comparison with metronidazole.

A new antiprotozoal agent, 1-methylsulphonyl-3-(1-methyl-5-nitro-2-imidazolyl)-2-imidazolidinone (Go-10213) has a distinct advantage over metronidazole when their respective neuropharmacological effects on central and peripheral nervous functions are compared in different animal species. The results show that at equivalent dosage schedules with repeated high dosages, Go-10213 is devoid of adverse central and peripheral neural effects in monkeys; cats and dogs, whereas unequivocal evidence of metronidazole neurotoxicity was obtained in all the three species. Go-10213 compares favourably with metronidazole in animal tests for cardiovascular tolerability.

Animals↗
PubMed1982

Behavioral and electrical correlates of absence seizures induced by thalamic stimulation in juvenile rhesus monkeys with frontal aluminum hydroxide implants: a pharmacologic evaluation.

A new method for producing electro-clinical correlates of absence seizures (petit mal epilepsy) in conscious juvenile rhesus monkeys is described. A behavioral arrest reaction associated with concomitant 2 1/2 to 3 Hz spike and wave electroencephalograph (EEG) after discharge pattern, was obtained by thalamic stimulation in monkeys with bilaterally symmetric aluminum hydroxide (Al(OH)3) lesions in anterior premotor cortical areas. The characteristic behavioral and EEG features associated with absence seizures appeared reproducibly, 63 +/- 5 days after aluminum hydroxide cortical implantation. This test system distinguishes between anticonvulsants that are effective in generalized seizures of the absence type and anticonvulsant drugs that are effective in focal seizures. Clinically useful anti-absence drugs, such as ethosuximide, sodium valproate, clonazepam, and trimethadione, are effective in this model. Diphenylhydantoin, which is contraindicated in absence states, increases the spike and wave after-discharge pattern. The limitations, advantages, and potential usefulness of this model in predicting anti-absence activity as well as the incidence of side effects of new drugs is discussed.

Aluminum Hydroxide↗
PubMed1981

Pharmacology of 8-aminoquinolines.

The 8-aminoquinolines were the first group of compounds to be synthesized specifically for their antimalarial activity. A large-scale research programme in the United States of America in the 1940s produced three new antimalarial drugs-pentaquine, isopentaquine, and primaquine -of which primaquine was the most effective. This article reviews knowledge on the activity of these 8-aminoquinolines against all stages of the malaria parasite and suggests their possible modes of action. The toxic effects and possible causal mechanisms are also outlined.

Aminoquinolines↗
PubMed1981

On the mechanism of action of an adrenergic blocking guanidine (CG8345-Go).

CG 8345 depletes noradrenaline stores in the rat, cat and dog tissues at a dose range of 1--50 mg/kg p.o. Unlike guanethidine there is no marked difference in the depleting effect of CG 8345 when given orally or intraperitoneally. The effect on the noradrenaline stores is longer lasting in cats and dogs as compared to rat. Like guanethidine CG 8345 releases H3-NA from the rat heart mainly in the form of bases. The compound gets accumulated into the sympathetically innervated organs by a specific uptake process which is similar to noradrenaline "pump" mechanism from where it can be released by reserpine. CG 8345 is stored in the same storage sites as noradrenaline in the rat heart.

Amphetamine↗
PubMed1980

Participation of adrenal medulla in 6-amino-nicotinamide-induced hyperglycaemia in the rat.

In fasted rats 6-aminonicotinamide (6-AN) produced delayed hyperglycaemia, the peak effect being seen by 7 h. Fasting plasma insulin concentrations were not significantly altered but liver glycogen concentrations were decreased following treatment with 6-AN. Adrenalectomy, demedullation and pretreatment with reserpine, phentolamine, nicotinamide and nicotinic acid completely blocked the hyperglycaemic response whereas guanethidine and propranolol or oxprenolol were ineffective. Catecholamine concentrations in the adrenal venous plasma were markedly increased by treatment with 6-AN, the peak effect being seen by 5 h. It is concluded that adrenal medullary release, which is slow in onset, is mainly responsible for the development of sustained hyperglycaemia in the rat.

6-Aminonicotinamide↗