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L Saiani

Publications and source records attributed to L Saiani.

13 recordsLinked to original sources
PubMed1984

Purification and characterization of a bungarotoxin polypeptide which blocks nicotinic receptor function in primary culture of adrenal chromaffin cells.

In primary cultures of bovine chromaffin cells, commercially available preparations of alpha-bungarotoxin inhibit the acetylcholine (ACh)- or nicotine-evoked release of endogenous catecholamines. The potency of different lots of alpha-bungarotoxin is not related to the alpha-bungarotoxin peptide content but to that of another peptide (termed P-4 bungarotoxin) present as an impurity in the alpha-bungarotoxin preparations. P-4 Bungarotoxin was isolated and purified to homogeneity by high-pressure liquid chromatography (HPLC). Homogeneity was established by a variety of means, including polyacrylamide gel electrophoresis, HPLC, end carboxy group analysis and NH2-terminal amino acid sequence. Purified P-4 bungarotoxin contains approximately 121 amino acid residues, and it is different in its amino composition, molecular weight, and amino acid sequence from alpha-bungarotoxin and beta-bungarotoxin. P-4 Bungarotoxin (IC50 congruent to 1 nM) blocked the ACh-induced release of endogenous catecholamines but failed to block the KCl-induced catecholamine release. Although P-4 bungarotoxin is endowed with phospholipase A2 activity, its effect on ACh-evoked catecholamine release persists when the phospholipase activity is blocked (99.9%) by treatment of the toxin with p-bromophenacyl bromide. P-4 Bungarotoxin may represent a useful tool with which to study nicotinic receptor function in sympathetic and central nervous system neurons.

Acetylcholine↗
PubMed1983

Cotransmitters: pharmacological implications.

The discovery that two or more neuroactive substances coexist in the same nerve terminal suggests that two or more neuroactive compounds can be released by nerve impulses simultaneously and probably act cooperatively at postsynaptic sites. This interaction changes the models of synaptic transmission we have used in the past and imposes a reevaluation of current understanding of synaptic pharmacology. Neuroactive substances co-existing in the same axon terminal can function as "primary transmitter" if they activate the receptor-transducer system or as "cotransmitter" if they modulate the gain of the system. Two examples of synaptic mechanisms in which two neuroactive substances coexisting in the same axon terminal appear to function as primary transmitter and cotransmitter are discussed. These examples are: 1. the modulation of the function of nicotinic receptors of chromaffin cells by endogenous opiate peptides stored in the splanchnic nerve and 2. the modulation of GABA receptor function by benzodiazepines. The understanding of the mechanisms by which primary transmitter and cotransmitter interact at the postsynaptic site may be of obvious importance in elucidating the integrative and discriminative function of the nervous system, in interpreting the action of drugs and in developing new therapeutic agents devoid of untoward side effects.

Animals↗
PubMed1983

Modulation of nicotinic receptor function by opiate recognition sites highly selective for Met5-enkephalin[Arg6Phe7].

Adrenal medullary cells contain opiate recognition sites that cannot be classified with any of the accepted conventional criteria. In primary cultures of bovine adrenal chromaffin cells, stimulation of nicotinic receptors by acetylcholine causes an increase in the release of catecholamines. When the action of acetylcholine is studied in the presence of opiate receptor agonists, the acetylcholine secretory action is curtailed. The action of the opiates is stereoselective and is blocked by naloxone and diprenorphine. The blocking activity of each opiate correlates with its Ki for the displacing of [3H]etorphine bound to specific recognition sites of adrenal medulla. Enkephalin-like opiate peptides are stored in the splanchnic nerves; they appear to act as a cotransmitter because they decrease the gain at which nicotinic receptors operate. This regulation appears to involve a down-regulation of the nicotinic receptor recognition sites because these opiate peptides elicit a decrease in the Bmax of the specific binding to adrenal medullary membranes of a radioactive fraction of alpha-bungarotoxin, a compound that inhibits the action of acetylcholine in releasing catecholamines from chromaffin cells.

Acetylcholine↗
PubMed1981

Regulation of acetylcholine receptors by endogenous cotransmitters: studies of adrenal medulla.

The coexistence of neuropeptides and amine transmitters in the same neuron and the presence of postsynaptic receptors for these compounds invite speculation that the compounds may interact postsynaptically. To study this interaction, we selected the synapse between the splanchnic nerve and the chromaffin cells of adrenal medulla because the splanchnic nerve contains acetylcholine and neuropeptides (multiple molecular forms of enkephalin-like peptides), while the membranes of chromaffin cells contain receptors for acetylcholine and opiate peptides. When the opiate receptors are occupied by specific agonists, these agonists inhibit the expression of acetylcholine receptors. Both the acetylcholine binding and catecholamine release by acetylcholine were inhibited. It is suggested that peptides and acetylcholine coexisting in the splanchnic nerve might act as cotransmitters, there by modulating the sensitivity of acetylcholine receptors. Multiple molecular forms of enkephalin-like peptides are stored in chromaffin cells and are released by acetylcholine. A role for the opiate receptors in the modulation of the secretion of opiate peptides stored in chromaffin cells is not evident.

Adrenal Medulla↗
PubMed1980

Impairment of brain neurotransmitter receptors in aged rats.

Dopamine and gamma-aminobutyric acid (GABA) receptor functions have been measured in various brain areas of aged rats. [3H] Spiroperidol binding is decreased in various dopaminergic brain areas, particularly in striatum and tuberculum olfactorium. In striatum the number of binding sites for [3H] spiroperidol is similar in both groups of animals, while the affinity is reduced in senescent rats. Moreover, in the pituitary a 50% increase of [3H] spiroperidol binding was detected in the group of senescent animals. On the other hand, [3H] GABA binding is significantly decreased in substantia nigra and hypothalamus of aged rats, while it is unmodified in cerebral cortex, cerebellum, striatum and nucleus accumbens.

Aging↗
PubMed1979

Bromocriptine and lisuride stimulate the accumulation of cyclic AMP in intact slices but not in homogenates of rat neostriatum.

The effects of bromocriptine and lisuride on cyclic AMP concentrations in homogenates and in intact slices of rat neostriatum were investigated. Significant increases in cyclic AMP concentration were found after a 10-min exposure to bromocriptine and lisuride in striatal intact slices. On the contrary, as previously found, the two dopaminergic ergot derivatives did not stimulate dopamine-senstiive adenylate cyclase present in striatal homogenates. The stimulatory effects observed only in intact tissues were blocked by the specific dopamine receptor blocking agent fluphenazine. It is tempting to conclude that dopaminergic ergot derivatives have a site of action different from that stimulated by classic dopamine agonists in tissue homogenates.

Animals↗
PubMedDate not supplied

[Met5]-enkephalin-like peptides of the adrenal medulla: release by nerve stimulation and functional implications.

In adrenal chromaffin cells, various molecular forms of polypeptides cross-reacting with [met5]-enkephalin antisera are stored in granules together with catecholamines and soluble proteins. Splanchnic nerve stimulation increases the release of enkephalin-like peptides from the adrenal gland into the adrenal vein. The release of these peptides appears to be mediated by a cholinergic nicotinic receptor. Fractionation of plasma extracts on Bio-gel P-2 shows the presence of only low molecular weight peptides in the resting condition. The low molecular weight fraction contains mainly [met5]-enkephalin and [leu5]-enkephalin. When the splanchnic nerve is stimulated high and low molecular weight peptides are released and the amount of low molecular weight peptides in plasma is increased. The content of enkephalin-like peptides in adrenal venous plasma was similar in control and reserpinized dogs. Splanchnic nerve stimulation increased the peptide content but not the epinephrine content of plasma in reserpinized dogs. This also caused a fall of arterial blood pressure which could be prevented by pretreatment with naloxone. A decrease in blood pressure was also directly elicited by the injection of [met5]-enkephalin-[arg6-phe7]. The duration of the hypotensive effect of this peptide was prolonged by prior injection of captopril.

Adrenal Medulla↗