Neuropeptide effect

Fig. 3A, B Neuropeptide effects on anxiety-related behavioiu. A The oxytocin receptor antagonist (black bars) administered intracerebroventricularly (i.c.v.) increased indices of anxiety-related behaviour in pregnant rats as measured on the elevated plus maze. Entries into the closed arms indicate unchanged locomotor activity. B Prolactin is an anxiolytic neuropeptide in female rats as revealed by i.c.v. administration of synthetic prolactin (grey and black bars represent two different doses) and by antisense targeting of the prolactin receptor (R). Vehicle (white bars) vs mixed bases (grey bars) and antisense oligodeoxynu-cleotide (black bars). p<0.05 vs vehicle (white bars). (Adapted from Nemnann et al. 2000) and Torner et al. 2001)...

G.J. Boer and D.F. Swaab, Neuropeptide effects on brain development to be expected from behavioral teratology, Peptides, 6 (Suppl. 2) (1985) 21-28. 

Data demonstrating a neuropeptide effect on motility are scarce. In S. mansoni neither FMRFamide nor substance P have any effect on muscle tone or activity, however it is not clear that they are able to reach their putative target sites intact (5). Endogenous FMRFamide-like and substance P-like peptides have not yet been isolated and tested. 

Melatonin [73-31-4] C 2H N202 (31) has marked effects on circadian rhythm (11). Novel ligands for melatonin receptors such as (32) (12), C2yH2gN202, have affinities in the range of 10 Af, and have potential use as therapeutic agents in the treatment of the sleep disorders associated with jet lag. Such agents may also be usehil in the treatment of seasonal affective disorder (SAD), the depression associated with the winter months. Histamine (see Histamine and histamine antagonists), adenosine (see Nucleic acids), and neuropeptides such as corticotropin-like intermediate lobe peptide (CLIP) and vasoactive intestinal polypeptide (VIP) have also been reported to have sedative—hypnotic activities (7). 

Numerous neuropeptides are beheved to be involved with the transmission or inhibition of pain, and the hope is to utilize this approach as a strategy to induce analgesia. Substance P is reported to be a transmitter of nociceptive impulses (39), and therefore antagonists should be analgesic. Capsaicin [404-86-4], C2gH2yN02, is known to deplete substance P and cause analgesia (40), but its side effects are intolerable. Antagonists to bradykinin [58-82-2], a substance known to induce pain (41), have shown some success in preclinical trials. 

The first idea to consider is the effect of receptor density on sensitivity of a functional system to agonists. Clearly, if quanta of stimulus are delivered to the stimulus-response mechanism of a cell per activated receptor the amount of the total stimulus will be directly proportional to the number of receptors activated. Figure 5.8 shows Gi-protein-mediated responses of melanophores transiently transfected with cDNA for human neuropeptide Y-l receptors. As can be seen from this figure, increasing receptor expression (transfection with increasing concentrations of receptor cDNA) causes an increased potency and maximal response to the neuropeptide Y agonist PYY. 

FIGURE 5.10 Effects of co-expressed G-protein (G ) on neuropeptide NPY4 receptor responses (NPY-4). (a) Dose-response curves for NPY-4. Ordinates Xenopus laevis melanophore responses (increases light transmission). Ordinates logarithms of molar concentrations of neuropeptide Y peptide agonist PYY. Curves obtained after no co-transfection (labeled 0 jig) and co-transfection with cDNA for Gai6. Numbers next to the curves indicate jig of cDNA of Ga]g used for co-transfection, (b) Maximal response to neuropeptide Y (filled circles) and constitutive activity (open circles) as a function of pg cDNA of co-transfected G g. 

Appetite-stimulating. Neuropeptide modulators and gut hormones with orexigenic effects are neuropeptide Y (NPY), agouti-related protein (AGRP), melaninconcentrating hormone (MCH), endocannabinoids, galanin, ghrelin and others. 

Synaptic vesicles mediate the release of small molecules other than classical neurotransmitters and neuropeptides. Of these, zinc and ATP are the best characterized. NMDA and GABA receptors contain binding sites for zinc, and zinc exerts a direct effect on... 

Findings from animal studies suggest that neuropeptide Y (NPY) may be associated with ethanol consumption. NPY-deficient mice have increased alcohol consumption (Thiele et al. 1998), an effect that is mediated by the Y1 and Y2 receptors (Pandey et al. 2003 Thiele et al. 2000, 2002). It has been suggested that NPY Y1 agonists and Y2 antagonists may have promise in the treatment of alcoholism (Cowen et al. 2004). 

Kask, A, Rago, L and Harro, J (1998) Anxiolytic-like effect of neuropeptide Y (NPY) and NPY13-36 microinjected into vicinity of locus coeruleus in rats. Brain Res. 788 345-348. 

Effects of Amphetamine Analogs on Central Nervous System Neuropeptide Systems... 

This chapter discusses the responses of these extrapyramidal neuropeptide systems to the amphetamine analogs methamphetamine (METH), methylene dioxyamphetamine (MDA), and methylenedioxymethamphetamine (MDMA). These dmgs were selected for this study because they represent somewhat diverse mechanisms of action. While all three agents are able to enhance extrapyramidal serotonergic activity (Schmidt et al. 1987). only METH has been characterized as a substantial stimulant of the DA system. The effects of MDA and MDMA on extrapyramidal DA systems have not been well elucidated. Thus, evaluating and comparing the responses of the SP, NT, and Dyn extrapyramidal systems to these dmgs will help to determine the nature of the DA responses to METH, MDA, and MDMA administrations. 

Administrations of five injeetions of METH (15 mg/4cg/injection 6-hour intervals between injections) caused substantial increases in the striatal and nigral levels of all three neuropeptides examined in rats sacrificed 18 hours following treatment. Figures 1 to 3 present the effects of blocking the Dj and D2 dopaminergic receptors on the responses by these peptide systems... 

FIGURE 4. Effects of MDMA on extrapyramidal neuropeptide contents... 

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