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S H Synder

Publications and source records attributed to S H Synder.

17 recordsLinked to original sources

Upregulation of nitric oxide synthase and galanin message-associated peptide in hypothalamic magnocellular neurons after hypophysectomy. Immunohistochemical and in situ hybridization studies.

The expression of several bioactive molecules in magnocellular hypothalamic neurons is modified when the axons of these cells are transected. In this study we have evaluated by means of immunocytochemistry and in situ hybridization the effect of hypophysectomy on the expression of nitric oxide synthase (NOS)- and of galanin message-associated peptide (GMAP)-like immunoreactivities (-LIs) as well as on their respective mRNAs in hypothalamic magnocellular neurosecretory neurons. The results show a transient increase in NOS- and GMAP-LIs in magnocellular neurons of both the paraventricular and supraoptic nuclei when compared to normal animals. The maximal increase in staining was observed between 5 and 7 days, and by 14 days NOS-LI was back to normal levels, whereas strong GMAP-LI could still be detected in a few cells. A similar picture was observed for the NOS and GMAP mRNAs. The functional significance of the present findings is unclear, but they indicate a possible role of nitric oxide and GMAP in neurosecretory neurons after injury.

Amino Acid Oxidoreductases↗

Nitric oxide synthase-like immunoreactivity in lumbar dorsal root ganglia and spinal cord of rat and monkey and effect of peripheral axotomy.

With the immunofluorescence technique, nitric oxide synthase (NOS)-like immunoreactivity (LI) was found in a few medium-sized and small sensory neurons in lumbar (L) 4 and L5 dorsal root ganglia (DRG) of normal rat, and in most of these neurons, NOS-LI coexisted with calcitonin gene-related peptide and sometimes with substance P and galanin. NOS-immunoreactive nerve fibers, terminals and small neurons were also located in the dorsal horn of the segments 4 and 5 of the rat lumbar spinal cord with the highest density in inner lamina II. Many NOS-positive neurons and fibers were seen in the area around the central canal. A sparse network of NOS-immunoreactive nerve fibers was found in the ventral horn. After unilateral sciatic nerve cut in the rat, the number of NOS-positive neurons increased in the ipsilateral L4 and L5 DRGs, mainly in medium and small neurons, but also in some large neurons and very small neurons. NOS-LI could now also be seen in the ipsilateral dorsal roots, and in an increased number of fibers and terminals in both outer and inner lamina II of the ipsilateral dorsal horn. The number of NOS-immunoreactive neurons in lamina II of the ipsilateral dorsal horn was reduced. In the monkey L4 and L5 DRGs, many small neurons were NOS-immunoreactive, but only a few weakly stained nerve fibers and terminals were found in laminae I-IV of the dorsal horn at L4 and L5 lumbar levels. A few NOS-positive neurons were present in lamina X. The number of NOS-immunoreactive neurons was somewhat reduced in DRGs 14 days after peripheral axotomy, but no certain effect was seen in the dorsal horn. These results, together with earlier in situ hybridization studies, demonstrate that axotomy in rat induces a marked upregulation of NOS synthesis in primary sensory neurons, thus suggesting a role for NO in lesioned sensory neurons. In contrast, no such effect was recorded in monkey, perhaps indicating distinct species differences.

Amino Acid Oxidoreductases↗

Increased brain dopamine and dopamine receptors in schizophrenia.

In postmortem samples of caudate nucleus and nucleus accumbens from 48 schizophrenic patients, there were significant increases in both the maximum number of binding sites (Bmax) and the apparent dissociation constant (KD) for tritiated spiperone. The increase in apparent KD probably reflects the presence of residual neuroleptic drugs, but changes in Bmax for tritiated spiperone reflect genuine changes in receptor numbers. The increases in receptors were seen only in patients in whom neuroleptic medication had been maintained until the time of death, indicating that they may be entirely iatrogenic. Dopamine measurements for a larger series of schizophrenic and control cases (n greater than 60) show significantly increased concentrations in both the nucleus accumbens and caudate nucleus. The changes in dopamine were not obviously related to neuroleptic medication and, unlike the receptor changes, were most severe in younger patients.

Adolescent↗

Autoradiographic localization of adenosine receptors in rat brain using [3H]cyclohexyladenosine.

Adenosine (A1) receptor binding sites have been localized in rat brain by an in vitro light microscopic autoradiographic method. The binding of [3H]N6-cyclohexyladenosine to slide-mounted rat brain tissue sections has the characteristics of A1 receptors. It is saturable with high affinity and has appropriate pharmacology and stereospecificity. The highest densities of adenosine receptors occur in the molecular layer of the cerebellum, the molecular and polymorphic layers of the hippocampus and dentate gyrus, the medial geniculate body, certain thalamic nuclei, and the lateral septum. High densities also are observed in certain layers of the cerebral cortex, the piriform cortex, the caudate-putamen, the nucleus accumbens, and the granule cell layer of the cerebellum. Most white matter areas, as well as certain gray matter areas, such as the hypothalamus, have negligible receptor concentrations. These localizations suggest possible central nervous system sites of action of adenosine.

Adenosine↗

Adverse effects of anticholinergic antiparkinsonian drugs in tardive dyskinesia. An investigation of mechanism.

10 long-term schizophrenic patients with tardive dyskinesia were studied over 14 weeks and maintained on their usual neuroleptic medications while anticholinergic antiparkinson drugs were employed and then discontinued, and the cycle then repeated. Discontinuation of anticholinergic medications resulted in improvement in dyskinetic movements and vice versa. Estimation of haloperidol equivalents in serum at four times suggested that changes in severity of tardive dyskinesia were not caused by changes in blood levels of neuroleptics. Levels of pituitary hormones were also estimated at four times. Prolactin levels tended to diminish in men over the course of the experiment. Growth hormone and thyrotropin values were mainly stable. However, the growth hormone levels peaked during the final 'off anticholinergic' condition and thyrotropin levels were consistently elevated.

Adult↗

Relationship of neuroleptic drug effects at brain dopamine, serotonin, alpha-adrenergic, and histamine receptors to clinical potency.

The authors examined the potencies of 22 neuroleptic drugs competing for binding sites associated with dopamine, serotonin, alpha-adrenergic, and histamine receptors in brain membranes. They found that although many neuroleptics are quite potent in competing at several of these receptor sites, the average antipsychotic clinical potency correlates closely only with the drug affinity for dopamine receptors labeled by 3H-spiroperidol At clinically effective doses, however, substantial occupancy of serotonin, alpha-adrenergic, and histamine receptors often occurs and may account for some of the auxiliary actions of neuroleptics.

Animals↗

Opiate receptor binding affected differentially by opiates and opioid peptides.

The potencies of various opiates in displacing several 3H-opiate ligands' binding to rat membranes vary depending on the nature of the ligand. Whereas opiate antagonists, as well as the opioid peptides and some agonists (etorphine, levorphanol and phenazocine) display similar affinities in displacing either 3H-opiate or 3H-methionine enkephalin binding, other agonists (such as morphine and oxymorphone) are considerably (20-50 times) weaker in displacing 3H-enkephalin than 3H-dihydromorphine binding. These agonists also compete for 3H-enkephalin binding with shallow displacement curves, and are greatly weakened in displacing 3H-naloxone binding in the presence of sodium. These agonists differ from the other opiate classes by possessing a relatively hydrophilic component in their C-ring moieties which may provide a basis for the differential interactions of drugs with the opiate receptor.

Animals↗