cholecystokinin and Parkinson-Disease

Patients with Parkinson's disease (PD) may develop several non-motor symptoms such as psychosis, depression, cognitive impairment, autonomic disturbances and sleep disturbances. Psychosis is one of the common non-motor symptoms, which commonly manifests as visual hallucinations and minor hallucinations such as sense of passage and presence. Though long-term dopaminergic therapy, longer duration of PD and cognitive impairment have been described as risk factors for emergence of psychosis in PD, predicting psychosis in PD remains challenging. Multiple studies have explored the genetic basis of psychosis in PD by studying polymorphisms of several genes. Most of the studies have focused on apolipoprotein E polymorphism followed by polymorphisms in cholecystokinin (CCK) system, dopamine receptors and transporters, HOMER gene, serotonin, catechol-o-methyltransferase, angiotensin converting enzyme and tau. Other than the studies on polymorphisms of CCK, most of the studies have reported conflicting results regarding association with psychosis in PD. Three out of four studies on CCK polymorphism have reported significant association of -45C>T polymorphism with the presence of hallucinations. The discrepancies in the results across the studies reviewed are possibly due to racial differences as well as differences in the patient characteristics. This review critically analyzes the published studies on genetic polymorphisms in patients with PD and psychosis.

Topics: Apolipoproteins E; Catechol O-Methyltransferase; Cholecystokinin; Databases, Bibliographic; Homer Scaffolding Proteins; Humans; Parkinson Disease; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Psychotic Disorders; Receptors, Dopamine; Serotonin; tau Proteins

Parkinson's disease (PD) is associated with several non-motor symptoms, such as behavioral changes, urinary dysfunction, sleep disorders, fatigue and, above all, gastrointestinal (GI) dysfunction, including gastric dysmotility, constipation and anorectal dysfunction. Delayed gastric emptying, progressing to gastroparesis, is reported in up to 100% of patients with PD, and it occurs at all stages of the disease with severe consequences to the patient's quality of life. The presence of α-synuclein (α-syn) aggregates in myenteric neurons throughout the digestive tract, as well as morpho-functional alterations of the enteric nervous system (ENS), have been documented in PD. In particular, gastric dysmotility in PD has been associated with an impairment of the brain-gut axis, involving the efferent fibers of the vagal pathway projecting directly to the gastric myenteric plexus. The present review intends to provide an integrated overview of available knowledge on the possible role played by the ENS, considered as a semi-autonomous nervous network, in the pathophysiology of gastric dysmotility in PD. Particular attention has been paid review how translational evidence in humans and studies in pre-clinical models are allowing a better understanding of the functional, neurochemical and molecular alterations likely underlying gastric motor abnormalities occurring in PD.

Topics: alpha-Synuclein; Animals; Cholecystokinin; Efferent Pathways; Enteric Nervous System; Gastric Emptying; Gastrointestinal Motility; Gastroparesis; Humans; Mice; Mice, Transgenic; Models, Neurological; Neuromuscular Junction; Oxidopamine; Parkinson Disease; Parkinsonian Disorders; Protein Aggregates; Rats; Rotenone; Translational Research, Biomedical; Vagus Nerve

Psychotic symptoms are frequent and disabling in patients with Parkinson's disease (PD). Methodological issues in the epidemiology of PD associated psychosis (PDP) include differences in the symptoms assessed, the methods of assessment, and the selection of patients. Most studies are prospective clinic-based cross-sectional studies providing point prevalence rates in samples on dopaminergic treatment. Visual hallucinations are present in about one quarter to one third of the patients, auditory in up to 20%. Tactile/somatic, and olfactory hallucinations are usually not systematically sought. Minor phenomena such as sense of presence and visual illusions affect 17 to 72% of the patients, and delusions about 5%. Lifetime prevalence of visual hallucinations reaches approximately 50%. Prospective longitudinal cohort studies suggest that hallucinations persist and worsen in individual patients, and that their prevalence increases with time. A facilitating role of treatment on PDP is demonstrated at least for dopaminergic agonists, but there is no simple dose-effect relationship between dopaminergic treatment and the presence or severity of hallucinations. The main endogenous non-modifiable risk factor is cognitive impairment. Other associated factors include older age/longer duration of PD, disease severity, altered dream phenomena, daytime somnolence, and possibly depression and dysautonomia. PDP reduces quality of life in patients and increases caregiver distress, and is an independent risk factor for nursing home placement and development of dementia.

Topics: Cholecystokinin; Cognition Disorders; Cross-Sectional Studies; Humans; Incidence; Longitudinal Studies; Parkinson Disease; Prevalence; Psychotic Disorders; Risk Factors

The nocebo effect is a phenomenon that is opposite to the placebo effect, whereby expectation of a negative outcome may lead to the worsening of a symptom. Thus far, its study has been limited by ethical constraints, particularly in patients, as a nocebo procedure is per se stressful and anxiogenic. It basically consists in delivering verbal suggestions of negative outcomes so that the subject expects clinical worsening. Although some natural nocebo situations do exist, such as the impact of negative diagnoses upon the patient and the patient's distrust in a therapy, the neurobiological mechanisms have been understood in the experimental setting under strictly controlled conditions. As for the placebo counterpart, the study of pain has been fruitful in recent years to understand both the neuroanatomical and the neurochemical bases of the nocebo effect. Recent experimental evidence indicates that negative verbal suggestions induce anticipatory anxiety about the impending pain increase, and this verbally-induced anxiety triggers the activation of cholecystokinin (CCK) which, in turn, facilitates pain transmission. CCK-antagonists have been found to block this anxiety-induced hyperalgesia, thus opening up the possibility of new therapeutic strategies whenever pain has an important anxiety component. Other conditions, such as Parkinson's disease, although less studied, have been found to be affected by nocebo suggestions as well. All these findings underscore the important role of cognition in the therapeutic outcome, and suggest that nocebo and nocebo-related effects might represent a point of vulnerability both in the course of a disease and in the response to a therapy.

Topics: Animals; Brain; Cholecystokinin; Cognition; Emotions; Fear; Humans; Hyperalgesia; Magnetic Resonance Imaging; Pain; Parkinson Disease

In recent years, a number of new molecules, particularly peptides, have been identified as putative neurotransmitters. The basal ganglia, is especially rich in a number of classical transmitter molecules, amino acids and neuropeptides considered to function in neurotransmission. These include: the well-described terminal fields in the striatum which originate from the brain stem and contain the monoamines, dopamine and serotonin; amino acid containing axons projecting from the cortex and thalamus; striatal cholinergic and peptide-positive interneurons; and amino acid and peptide containing projection neurons to the globus pallidus and substantia nigra. Two amino acids, glutamate and aspartate, are considered to provide excitatory input to the striatum while gamma aminobutyric acid is thought to mediate inhibitory output. Neuropeptides which are richly concentrated in the basal ganglia include, enkephalin, dynorphin, substance P, somatostatin, neuropeptide Y and cholincystokinease. Changes in many of these peptide levels have recently been associated with a number of basal ganglia disorders.

Topics: Acetylcholine; Amino Acids; Animals; Basal Ganglia; Cholecystokinin; Dopamine; Endorphins; Humans; Huntington Disease; Neuropeptides; Neurotransmitter Agents; Parkinson Disease; Primates; Serotonin

Neuropeptides are sufficiently stable to allow valid radioimmunoassay of peptide concentrations in post-mortem human nervous tissue and in human cerebrospinal fluid. Studies have now documented abnormalities of peptide concentrations in degenerative diseases of the brain. Somatostatin concentration is reduced in the hippocampus and neocortex of patients dying with Alzheimer's type dementia. In Huntington's disease, there are reduced concentrations of substance P, met-enkephalin and cholecystokinin in the basal ganglia; in contrast the concentrations of somatostatin and TRH are increased. Immunocytochemical and experimental lesion studies are underway in an attempt to localize the peptide-containing cells affected by these disorders; and the potential role of alterations in neuropeptide function in the pathogenesis, clinical manifestations and therapy of these illnesses is of great interest. Although alterations of CSF peptide concentrations have been reported in a variety of human diseases, interpretation of these results requires knowledge of the origin and disposition of CSF peptides. Future research into the pathology of peptidergic systems will depend on the development of specific peptide antagonists to probe dynamic aspects of peptide function and on the application of the tools of molecular biology, such as specific mRNA assays, to human material.

Topics: Alzheimer Disease; Animals; Brain; Cholecystokinin; Choline O-Acetyltransferase; Endorphins; Epilepsy; Forecasting; Histocytochemistry; Humans; Huntington Disease; Migraine Disorders; Nerve Tissue Proteins; Nervous System Diseases; Pain; Parkinson Disease; Radioimmunoassay; Somatostatin; Substance P; Thyrotropin-Releasing Hormone; Tissue Distribution; Vasopressins

In Huntington's disease, there is a decrease of the neuropeptides, substance P, enkephalins, and cholecystokinin in the striatonigral system, whereas in Parkinson's disease an increase of substance P is found in the substantia nigra. Several neuropeptides should be involved in Alzheimer's disease: substance P, endorphins, vasopressin, ACTH, somatostatin, vasoactive intestinal peptide, cholecystokinin, neurotensin, delta sleep-inducing peptide. Alterations of substance P, vasoactive intestinal peptide, cholecystokinin, somatostatin, and endorphins may be related to the pathophysiology of schizophrenia. Delta sleep-inducing peptide may interfere in addiction pathology.

Topics: Alzheimer Disease; Brain Mapping; Central Nervous System Diseases; Cholecystokinin; Enkephalins; Humans; Huntington Disease; Limbic System; Nerve Tissue Proteins; Neurotransmitter Agents; Parkinson Disease; Schizophrenia; Substance P; Substance-Related Disorders

Cholecystokinin (CCK) is a neuropeptide which is colocalized with dopamine (DA) in neurons of the mesolimbic-frontocortical and nigrostriatal DA system. In animals CCK enhances DA activity in these systems.. The present study examined the effects of a single intranasal administration of CCK-8 on auditory brain potential (AEP) signs of cognitive processing and on motor performance in patients with Parkinson's disease (PD), known to originate from degeneration of DA neurons primarily in the nigrostriatal DA system.. Thirteen PD patients were examined after medication withdrawal, on two occasions after administration of placebo and 25 microg CCK-8, and compared with healthy controls matched for age and sex. AEPs were recorded while subjects performed an attention task (oddball paradigm).. In the placebo condition, AEPs in the PD patients did not show marked alteration but were rather comparable to those in the controls. In healthy controls, CCK-8 enhanced the P3 complex ( P<0.05) and shortened latencies of the N2 and P3 components of the AEP evoked by task relevant target stimuli ( P<0.05). Contrary to expectations, in PD patients these AEP components were distinctly delayed after CCK-8 ( P<0.05). Motor performance was not changed by CCK-8 in PD patients or in controls.. Data indicate a deleterious rather than beneficial effect of CCK on cognitive processing in PD patients that might result from a prevailing effect of the neuropeptide on transmitter systems (e.g. GABAergic) other than the DA system.

Topics: Aged; Brain; Cholecystokinin; Cognition; Double-Blind Method; Evoked Potentials, Auditory; Female; Humans; Male; Middle Aged; Motor Activity; Parkinson Disease; Reaction Time

Proglumide, a cholecystokinin antagonist, did not improve Parkinson's disease in a preliminary drug treatment trial.

Topics: Aged; Cholecystokinin; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Proglumide

Topics: Adult; Aged; Ceruletide; Cholecystokinin; Clinical Trials as Topic; Dopamine; Double-Blind Method; Female; Humans; Male; Middle Aged; Parkinson Disease; Schizophrenia

Topics: Animals; Ceruletide; Cholecystokinin; Clinical Trials as Topic; Feeding Behavior; Humans; Motor Activity; Parkinson Disease; Receptors, Dopamine; Schizophrenia; Sincalide; Synapses

Parkinson's disease (PD) is the second most common neurodegenerative disease, and no treatment is available to stop its progression. Studies have shown that the colonic pathology of PD precedes that of the brain. The 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and the human A53T α-synuclein (α-syn) transgenic PD mouse model show colonic pathology and intestinal dopaminergic neuronal damage, which is comparable to the intestinal pathology of PD. Cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1), which are brain-gut peptides, have neurotrophic and anti-inflammatory properties. Two GLP-1R agonists have already shown robust effects in phase II trials in PD patients. However, whether they have beneficial effects on colonic pathology in PD remains unclear. In this study, MPTP-treated mice and human A53T α-syn transgenic mice were intraperitoneally injected with a CCK analogue or Liraglutide, a GLP-1 analogue, once a day for 5 weeks. Levels of colonic epithelial tight junction proteins including occludin and zonula occludens-1 (ZO-1), inflammatory biomarkers including inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α), brain-derived neurotrophic factor (BDNF), tyrosine hydroxylase (TH) and α-syn were analyzed. The results show that the CCK analogue and Liraglutide both restored the disruption of intestinal tight junction, reduced colonic inflammation, inhibited colonic dopaminergic neurons reduction and the accumulation of α-syn oligomers in the colon of both PD mice models. This study suggested that CCK or GLP-1 analogues could be beneficial to the improvement of leaky gut barrier, inflammation, dopaminergic neuron impairment and accumulation of α-syn in the colon of PD patients.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; alpha-Synuclein; Animals; Cholecystokinin; Colon; Disease Models, Animal; Dopaminergic Neurons; Glucagon-Like Peptide 1; Humans; Inflammation; Liraglutide; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurodegenerative Diseases; Parkinson Disease; Tight Junctions

Topics: Asian People; Case-Control Studies; Cholecystokinin; Female; Gene Frequency; Genetic Association Studies; Genotype; Hallucinations; Humans; Longitudinal Studies; Male; Parkinson Disease; Polymorphism, Single Nucleotide

The principal causative pathology of Parkinson disease is the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta projecting to the striatum in the brain. The information regarding the expression of neuropeptides in parkinsonism is very limited. Here we have elucidated striatal neuropeptide mechanisms in experimental parkinsonism using the unilateral 6-hydroxydopamine model to degenerate dopamine neurons. A thoroughly controlled sample preparation technique together with a peptidomics approach and targeted neuropeptide sequence collections enabled sensitive detection, identification, and relative quantitation of a great number of endogenous neuropeptides. Previously not recognized alterations in neuropeptide levels were identified in the unilateral lesioned mice with or without subchronic 3,4-dihydroxy-L-phenylalanine administration, the conventional treatment of Parkinson disease. Several of these peptides originated from the same precursor such as secretogranin-1, somatostatin, prodynorphin, and cholecystokinin. Disease-related biotransformation of precursors into individual peptides was observed in the experimental model of Parkinson disease. Several previously unreported potentially biologically active peptides were also identified from the striatal samples. This study provides further evidence that neuropeptides take part in mediating the central nervous system failure associated with Parkinson disease.

Topics: Amino Acid Sequence; Animals; Cholecystokinin; Chromogranin B; Disease Models, Animal; Enkephalins; Mice; Molecular Sequence Data; Neostriatum; Oxidopamine; Parkinson Disease; Peptides; Postmortem Changes; Protein Precursors; Reproducibility of Results; Somatostatin; Tissue Extracts; Tyrosine 3-Monooxygenase

Parkinson's disease (PD) is an age-related neurodegenerative disease characterized by a progressive motor disorder, but frequently is accompanied by autonomic symptoms such as hypotension. Together with the decrease of dopamine, significant decreases in aminopeptidase activities have been reported in PD brains. However, up to date there are no studies about changes of aminopeptidase activities in plasma of PD patients. We studied plasma activities of alanyl-, aspartyl-(AspAP), cystinyl-(CysAP) and glutamyl-aminopeptidase (GluAP) in two groups of subjects: control (n=41) and PD (n=48). Plasma activities of AspAP, CysAP, and GluAP showed significant decreases of 24.9% (p<0.05), 39.4% (p<0.01) and 33.3% (p<0.01), respectively, in PD group. These aminopeptidases are involved in the metabolism of circulating peptides such as the ones of the renin-angiotensin system. The importance of aminopeptidases in striatal dopamine content and in neuroendocrine system in PD is discussed.

Topics: Aged; Aminopeptidases; Angiotensins; Cholecystokinin; Dopamine; Enkephalins; Female; Humans; Male; Middle Aged; Neurotensin; Parkinson Disease; Substance P; Vasopressins

Hallucinations in patients with Parkinson disease (PD), occurring in about one third of those receiving long-term dopaminergic therapy, contribute to morbidity and mortality. In matched Chinese PD subjects with and without hallucinations, the presence of the -45 C/T locus in the cholecystokinin (CCK) gene, particularly when combined with the CCK receptor, CCKAR (cholecystokinin A receptor), C polymorphism, was associated with increased hallucination risk. Because CCK gene polymorphisms vary across ethnic groups, the presence of similar associations in white PD subjects merits investigation.. To determine whether polymorphisms of CCK and CCK receptor genes are associated with hallucinations in white PD subjects.. Case-control study of PD subjects with and without chronic hallucinations matched for age and dopaminergic medication. Genomic DNA was analyzed for CCK, CCKAR, and CCKBR (cholecystokinin B receptor) polymorphisms by polymerase chain reaction. Genotype distributions and allele frequencies were compared between groups and in matched pairs.. Comparing matched pairs, we found more frequent representation of the CCK T allele in hallucinating PD subjects, although this finding was not statistically significant (P =.06). Of 5 cases with both CCK T and CCKAR C alleles, 4 were hallucinators. Cases and controls did not differ in CCKAR or CCKBR polymorphisms.. Our study supports a previous association of hallucinations in PD subjects with the CCK T allele and the combined CCK T and CCKAR C allele, suggesting that the CCK system may influence the development of hallucinations in PD subjects. The lower representation of the T allele in our white sample limited our statistical power. Further assessment of the T allele as a risk factor for hallucinations would include longitudinal study of nonhallucinators to detect the evolution of hallucinations relative to T allele frequency.

Topics: Aged; Aged, 80 and over; Alleles; Case-Control Studies; Cholecystokinin; Dopamine Agents; Female; Gene Frequency; Hallucinations; Humans; Male; Middle Aged; Parkinson Disease; Polymorphism, Genetic; Receptors, Cholecystokinin

Cholecystokinin modulates the release of dopamine and dopamine-related behaviours in the mesolimbic pathway, where cholecystokinin and dopamine coexist in dopaminergic neurones. Because cholecystokinin and its receptors (A and B) have a functional interaction with dopaminergic neurotransmission, alterations in them may constitute a predisposition for Parkinson's disease. We performed a case-control study to investigate the association between the cholecystokinin system and Parkinson's disease using genetic markers for three genes: cholecystokinin and its two receptors (A and B). One hundred and sixty patients with Parkinson's disease and 160 controls, matched for age, gender, ethnic origin and area of residence, were recruited. Cholecystokinin -45C>T, cholecystokinin-A receptor 779T>C and cholecystokinin-B receptor 1550G>A gene polymorphisms were studied using polymerase chain reaction-restriction fragment length polymorphism analyses. These three gene polymorphisms showed no correlation with risk of Parkinson's disease; however, the cholecystokinin CT/TT genotype was associated with a 4.429-fold increased risk for visual hallucinations in Parkinson's disease. Cholecystokinin-A receptor and B receptor polymorphisms, considered alone, showed no correlation with hallucinations in Parkinson's disease; however, a combined effect was found in patients with hallucinations harboring both the cholecystokinin CT/TT and cholecystokinin-A receptor TC/CC genotypes. Parkinson's disease patients harboring this genotype have a 5.922-fold increased risk for developing visual hallucinations. These results suggest that, in Chinese, visual hallucinations in Parkinson's disease are associated with cholecystokinin -45C>T polymorphism, and this association was still observed in the presence of the cholecystokinin-A receptor TC/CC genotype, indicating a possible interaction of these two genes in the visual hallucinogenesis in Parkinson's disease.

Topics: Case-Control Studies; Cholecystokinin; Female; Hallucinations; Humans; Male; Parkinson Disease; Polymorphism, Genetic; Receptor, Cholecystokinin A; Receptor, Cholecystokinin B

Various factors, including the orphan nuclear receptor Nurr1, have been implicated in dopamine biosynthesis, but many of the specific events involved in this process have to be determined. Using genetic manipulations in mice, the obligatory role for Nurr1 in dopamine (DA) biosynthesis has been documented; however, the mechanism remains unclear. DA biosynthetic enzymes, transporters and receptors are absent in the substantia nigra (SN) and the ventral tegmental area (VTA) of Nurr1-null neonates. The current study establishes that the loss of Nurr1 function does not affect the normal ventralization of neuroepithelial cells to the ventral midbrain, their differentiation into neurons, and their topographical pattern in the SN and VTA. Futhermore, the absence of Nurr1 does not affect the survival of these DA precursor cells in the ventral midbrain, as determined by quantitative analysis of cells, expressing the general neuronal nuclear marker (NeuN) and the TUNEL assay for apoptosis. These neurons express cholecystokinin (CCK), a co-transmitter of dopaminergic neurons in this area. The untranslated exon 1-2 of the Nurr1 gene, which remains intact after homologous recombination, revealed the presence of dopaminergic precursors in the ventral midbrain of the Nurr1-null mice. In addition, these neurons establish their nigrostriatal projections, as shown by axonal transport of a fluorescent tracer, DiI. These results provide evidence that Nurr1 is essential for terminal differentiation of the dopaminergic neurons in the ventral midbrain but does not affect the early steps of their neurogenesis, migration, survival and striatal projections. Our findings suggest that activation of Nurr1 might be therapeutically useful in Parkinson's disease.

Topics: Animals; Animals, Newborn; Apoptosis; Axonal Transport; Cell Count; Cell Differentiation; Cell Movement; Cell Survival; Cholecystokinin; DNA-Binding Proteins; Dopamine; Exons; Homeodomain Proteins; Humans; In Situ Hybridization; In Situ Nick-End Labeling; Mice; Mice, Knockout; Neurons; Neuropeptides; Nuclear Receptor Subfamily 4, Group A, Member 2; Parkinson Disease; Recombination, Genetic; RNA, Messenger; Stem Cells; Substantia Nigra; Transcription Factors; Tyrosine 3-Monooxygenase; Ventral Tegmental Area

Parkinson's disease (PD) is characterized by major alterations of neurotransmitter activity due to damage of the substantia nigra. Changes in neuropeptide concentration within the basal ganglia may play an important role in the putative dopaminergic-peptidergic interactions associated with the disease. Cholecystokinin (CCK) modulates the release of dopamine in the mesolimbic pathway and affects dopamine-related behavior. We analyzed genetic variations in the CCK gene, in both the coding and promoter region, in order to investigate the role of polymorphism in idiopathic PD. Four polymorphic sites of the CCK gene (-196G/A, -45C/T, 1270C/G, 6662C/T) were found in PD patients and controls. Complete linkage disequilibrium was observed between the -45 locus and the 1270 locus, and also a possible linkage disequilibrium was found between the -45 and -196 loci. A significant difference was found in the distributions of three identified genotypes at the -45 locus between 116 PD patients and 95 age-matched control subjects (chi2 = 7.95, p = 0.018, Bonferroni correction; p = 0.054). In addition, a significant difference was obtained amongst the three genotypic groups at the -45 locus when compared between PD patients who experienced hallucinations (n = 23) and those (n = 93) who did not (chi2 = 8.08, p = 0.018, Bonferroni correction, p = 0.126). Our data suggested that mutations at the -45 locus in the promoter region of the CCK gene may influence vulnerability to hallucinations in PD patients treated with L-dopa.

Topics: Age of Onset; Aged; Cholecystokinin; Data Interpretation, Statistical; DNA Mutational Analysis; Female; Genetic Variation; Humans; Male; Parkinson Disease; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Single-Stranded Conformational; Promoter Regions, Genetic

Substance P (SP), Met-enkephalin (Met-enk) and cholecystokinin-8-S (CCK-8-S) were measured by a combined HPLC/RIA method in the caudate nucleus and anterior putamen from controls and from Parkinson's disease (PD) patients. SP levels were reduced in caudate in PD, but unchanged in putamen. No differences in Met-enk content were found in parkinsonians compared to controls. However, a significant correlation between DA and Met-enk levels in caudate nucleus from PD was observed. The concentration of CCK-8-S was unaltered in caudate nucleus or putamen in PD. The decrease in caudate nucleus SP levels might be related to the decrease in nigral SP levels in PD, while the reduction in Met-enk levels appears to be a feature of a subgroup of parkinsonian patients.

Topics: Aged; Cholecystokinin; Chromatography, High Pressure Liquid; Corpus Striatum; Dopamine; Enkephalin, Methionine; Female; Humans; Male; Neuropeptides; Parkinson Disease; Radioimmunoassay; Substance P

The close relationship of cholecystokinin peptides with some of the dopamine pathways and the limbic system suggests a putative role for these peptides in the pathophysiology of neuropsychiatric disorders such as Parkinson's disease, manic-depression and schizophrenia. By use of radioimmunoassay, we report a significant decrease in cholecystokinin-immunoreactivity in the cerebrospinal fluid of patients with bipolar manic-depression and untreated schizophrenia in comparison to control subjects.

Topics: Adult; Bipolar Disorder; Cholecystokinin; Depressive Disorder; Female; Humans; Male; Mental Disorders; Middle Aged; Parkinson Disease; Schizophrenia

Topics: alpha-Methyltyrosine; Animals; Brain; Cholecystokinin; Dopamine; Drug Interactions; Extrapyramidal Tracts; Haloperidol; Male; Methyltyrosines; Parkinson Disease; Rats; Rats, Inbred Strains; Reserpine

The regional distribution of immunoassayable CCK-8 was determined in 12 regions of control and parkinsonian human brain, with specific attention to the possible regional coexistence of CCK-8 with dopamine. In Parkinson's disease, CCK-8-I levels were only decreased in the substantia nigra where dopamine cell bodies lie, and not in striatal and corticolimbic dopamine projecting areas. Our results suggest that the major proportion of dopaminergic neurones degenerated in Parkinson's disease may not contain the CCK-8 peptide.

Topics: Appetite Depressants; Autopsy; Brain; Brain Chemistry; Cholecystokinin; Humans; Parkinson Disease; Peptide Fragments; Sincalide; Substantia Nigra; Tissue Distribution