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At least 1,315 records · Page 73Linked to original sources
PubMed1991

Phosphoinositide hydrolysis linked 5-HT2 receptors in fibroblasts from choroid plexus.

A serotonin (5-HT)-mediated phosphoinositide hydrolysis response was characterized in fibroblasts cultured from rabbit choroid plexus. 5-HT elicited a maximum 8-fold increase in [3H]inositol-phosphate ([3H]IP) formation, while the partial agonists, (+)-lysergic acid diethylamide and (-)-1-(4-bromo-2,5-dimethyoxyphenyl)-2-aminopropane caused 2- and 5-fold increases, respectively. Mianserin, ketanserin, and spiperone were equipotent at blocking the 5-HT-mediated response. Thus, agonist and antagonist profiles indicate interactions with 5-HT2 receptors.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1992

5-HT2 receptors in the nucleus tractus solitarius: characterisation and role in cardiovascular regulation in the rat.

The effects of the local application of drugs acting on 5-HT2 receptors in the nucleus tractus solitarius (NTS) on the heart rate and blood pressure were investigated in normal and nodose ganglionectomized anaesthetized rats. The unilateral micro-injection of an agonist such as 2,5-dimethoxy-3-bromo-amphetamine (DOB) (0.1-0.5 pmol) or 2,5-dimethoxy-3-nitroamphetamine (DON) (0.1-0.5 pmol) produced a dose-dependent hypotension and bradycardia in both intact and ganglionectomized animals. These cardiovascular effects were similar to those observed after the unilateral micro-injection of low doses (pmol) of 5-HT, and could be prevented by the prior micro-injections of the 5-HT2 antagonists ketanserin, ritanserin and piremperone. These findings support the hypothesis that 5-HT2 receptors within the NTS play a role in the reflex regulation of blood pressure. In addition, it was also observed that the micro-injection of subthreshold doses of 5-HT or DOB significantly enhanced the hypotension and bradycardia produced by the unilateral micro-injection of N-methyl-D-aspartate (NMDA). The potentiation of NMDA depressor effects by 5-HT or DOB could be totally prevented by ketanserin or piremperone, suggesting that 5-HT acting upon 5-HT2 receptors in the NTS may intervene in the reflex control of blood pressure by modulating the glutamatergic transmission.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1993

Towards an improved survival of rat brain neurons in culture by cerebrospinal fluid of patients with senile dementia of Alzheimer's type.

Neuronal cell survival was investigated in rat brain cortical cultures in the presence of increasing concentrations of human brain extracts or cerebrospinal fluid (CSF) from control and Senile Dementia of Alzheimer's type (SDAT) patients. Using hippocampal brain extracts, converted 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) was compared to the content of the neuronal marker MAP2 in foetal rat brain neuronal cultures in order to test converted MTT as a quantitative parameter for neuronal cell survival. A significant correlation was found between both parameters. SDAT frontal cortex brain extracts induced a two four-fold increase in neuronal cell survival at 25 to 125 micrograms protein extract, whereas control brain extracts induced at similar protein concentrations a decline in neuronal cell survival. The enhanced survival yielded by SDAT brain extracts was fully abolished in the presence of control brain extract. Control CSF concentration-dependently increased neuronal cell survival in postnatal rat brain neuronal cultures independent of the difference in the protein content of CSF samples and age of the patients. SDAT CSF also concentration-dependently enhanced neuronal cell survival, however, the effect was more pronounced compared to control CSF. These observations are in favour of the hypothesis that there might be a higher neurotrophic activity in SDAT brain tissue.

Adult↗
PubMed1984

Rectus femoris muscle grafts performed with and without vascular anastomosis: an experimental study in the rabbit.

To study the effect of vascular repair on muscle transplants, rectus femoris muscles in rabbits were grafted orthotopically with and without microsurgical blood vessel repair. The function and structure of the grafts were evaluated 90 days after operation. Contractile properties were measured in vivo. Muscle biopsies were stained for nerve and motor end-plate regeneration. The twitch tension and maximal tetanic tension returned respectively to 32 +/- 6% and 32 +/- 7% of control values in the vascular transplants. In the avascular transplants twitch tension and maximal tetanic tension were respectively 6 +/- 1% and 8 +/- 1% of control values. Poor regeneration of muscle fibres, infection, fibrosis and immature reinnervation were the reasons for failure of avascular transplants. The avascular muscle grafts had insufficient contractile properties and were more static than dynamic. In conclusion, large avascular muscle grafts should be avoided because of the likelihood of poor revascularisation with extensive ischaemic necrosis, resulting in scar tissue.

Animals↗
PubMed1987

Potent agonist activity of DOB at 5-HT2 receptors in guinea pig trachea.

DOB, 4-bromo-2,5-dimethyloxyamphetamine, a potent hallucinogen, displays high affinity for the 5-HT2 receptor in binding assays. Since 5-HT contractile responses in guinea pig trachea are mediated by 5-HT2 receptors, we assessed the activity of DOB and related analogs in this preparation. DOB acts as a partial 5-HT agonist with an EC50 = 25 nM and is blocked by the potent selective 5-HT2 receptor antagonists ketanserin, pirenperone and LY 53857, as is 5-HT. These findings indicate that DOB may be a useful agent in characterizing 5-HT2 receptor responses.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1988

Serotonergic regulation of noradrenergic coerulean neurons: electrophysiological evidence for the involvement of 5-HT2 receptors.

To determine the type of serotonergic receptor involved in the modulation of noradrenergic neuronal activity in the locus coeruleus, the effects of 4 systemically administered serotonergic drugs were tested on the firing rate of noradrenergic neurons in the locus coeruleus of rats under chloral hydrate anaesthesia. The serotonergic agonist, quipazine (1 mg/kg), and the selective 5-HT2 agonist, DOB (50-100 micrograms/kg), induced a pronounced decrease of the discharge frequency. This effect could be prevented or reversed by the selective 5-HT2 antagonist, ketanserin (4-8 mg/kg). Ketanserin alone and the 5-HT1 agonist, RU 24969, had no or a weak excitatory action on the neuronal activity of the locus coeruleus. We conclude that the serotonergic control of noradrenergic neurons in the locus coeruleus is mediated by post-synaptic 5-HT2 receptors because the quipazine-ketanserin effects on this unit activity persisted after depletion of serotonergic presynaptic stores.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1988

Indolealkylamine analogs share 5-HT2 binding characteristics with phenylalkylamine hallucinogens.

Twenty-one indolealkylamines, some of which are known to be psychoactive in man, were examined for their binding interactions with rat brain cortical 5-HT2 receptors labeled with the antagonist radioligand [3H]ketanserin in order to develop structure-activity relationships for binding at these sites. Features investigated included aromatic, alpha-methyl and terminal amine substituents. 4-Methoxy and 5-methoxy substitution impart a higher affinity than 6- or 7-methoxy substitution; a 7-hydroxyl group essentially abolishes affinity whereas a 7-methyl or 7-bromo group enhances affinity. alpha-Methylation has little effect on affinity and, in the one case examined, the S(+) isomer of alpha-methyltryptamine was essentially equipotent with its racemate and twice as potent as its R(-) enantiomer. Terminal amine methylation results in a small but progressive decrease in affinity in the order: primary amine greater than dimethylamine greater than diethylamine. Similarities were noted between these structural requirements for binding and those of the phenalkylamines. Selected compounds (5-methoxytryptamine, N,N-dimethyltryptamine, 5-methoxy-N,N-diethyltryptamine and 5-methoxy-N,N-dimethyltryptamine) were further examined by two-site analysis of displacement studies for [3H]ketanserin specific binding. Hill coefficients were significantly less than unity and computer-assisted analysis indicated that a two-site model better fit the data than a one-site model. In displacement studies using the putative agonist radioligand [3H]DOB to label 5-HT2 receptors affinities were 10-100-fold higher than those using [3H]ketanserin. These results are also consistent with earlier findings using psychoactive phenalkylamines in competition studies for radiolabelled 5-HT2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1985

Innervation of rabbit intrapulmonary neuroepithelial bodies. Quantitative and qualitative ultrastructural study after vagotomy.

The purpose of this study was to locate the cell bodies of origin of the intracorpuscular nerve endings of the intrapulmonary neuroepithelial bodies (NEB). Left infra- or supranodosal vagotomy was performed on 35 young rabbits. In control animals, the NEB innervation index (i.e. the ratio of the number of intracorpuscular nerve endings to the number of NEB corpuscular epithelial cells) was 0.3 in both left and right lungs. Left infranodosal vagotomy decreased the NEB innervation index in the left lung to 0.1 by 24 h postoperatively. Degenerating nerve endings displaying neurofilamentous hyperplasia, were found among the few surviving nerve endings. Left supranodosal vagotomy did not influence the innervation of the NEB of the left lung, even at 5 days postoperatively. In the right lungs, neither procedure had significant effects. These findings indicate that the NEB are predominantly innervated by sensory nerve fibers, derived from cell bodies in the nodose ganglion of the vagus nerve. This neuroanatomical argument corroborates our hypothesis that NEB represent intrapulmonary neuroreceptors.

Animals↗