rethinkPeptides Search
Menu
RethinkPeptides

Neuropeptides research

Explore studies of neuropeptides.

Filter by topic, method, and evidence

You can select more than one topic or evidence level.

Clear filters

RPEP-00020 · 1984

Anglerfish Produce Two Versions of the Same Brain Hormone Peptide

Two versions of somatostatin-28 were isolated from anglerfish tissue. Both came from the same gene, but one had a modified amino acid: 5-hydroxylysine at position 23. Mass spectrometry confirmed the two forms had molecular weights of 3,220 (hydroxylated) and 3,204 (non-hydroxylated). The 16-unit difference matches exactly what adding one oxygen atom would do. This was the first documented case of a hydroxylated peptide hormone. Before this, hydroxylysine was known almost exclusively from collagen (the protein that gives skin and bones their structure).

Andrews, P C; Hawke, D; Shively, J E; Dixon, J E · In Vitro

RPEP-00026 · 1985

How Thymosin and Other Immune Molecules Send Signals to the Brain

The paper argued that certain molecules made by immune cells can send signals directly to the brain. The authors named these 'immunotransmitters,' a new term for molecules that carry information from the immune system to the central nervous system (CNS). Examples include thymosin alpha 1 and thymosin beta 4 (peptides from the thymus gland), as well as ACTH (a stress hormone), TSH (thyroid hormone), and beta-endorphin (a natural painkiller) produced by lymphocytes (white blood cells). The review presented evidence that thymosin peptides can alter the hypothalamic-pituitary-adrenal (HPA) axis, which is the brain's master hormone control system. They also appeared to affect the gonadal (reproductive hormone) axis.

Hall, N R; McGillis, J P; Spangelo, B L; Goldstein, A L · Review

RPEP-00045 · 1987

Brain Opioid Peptides Changed Dramatically During Seizures in Rats

A single injection of kainic acid (1 microgram) into rat brains caused seizures lasting 3 to 6 hours. During seizures, hippocampal met-enkephalin dropped 31% and dynorphin A dropped 63%, suggesting these opioid peptides were being released. By 24 hours, levels returned to normal. By 48 hours, met-enkephalin surged to 270% of normal and dynorphin to 150%. The brain had ramped up production to replace what was used. The biosynthetic machinery confirmed this: mRNA for preproenkephalin (the genetic template for making enkephalin) jumped to 400% of control at 6 hours. The actual precursor protein followed at 24 hours, reaching 300% of control. The seizure-induced shaking behavior (wet-dog shakes) was directly linked to enkephalin. Naloxone (an opioid blocker) reduced the shaking. Anti-enkephalin antibodies also reduced it. Injecting enkephalin peptides into the hippocampus mimicked the shaking.

Hong, J S; Grimes, L; Kanamatsu, T; McGinty, J F · Animal Study

RPEP-00050 · 1987

Salt Stress Ramped Up Vasopressin, Oxytocin, and Dynorphin Gene Expression

Rats drinking 2% salt solution showed progressive increases in three neuropeptide mRNAs in the hypothalamus (a brain region controlling hormones): Vasopressin, oxytocin, and dynorphin mRNAs all increased in the magnocellular neurons of the supraoptic and paraventricular nuclei. These are the brain cells that make these peptide hormones. Enkephalin mRNA was not detectable in these brain areas under normal conditions. It only appeared after 12 days of salt loading or after the acute stress of a salt injection into the abdomen. Lactating mother rats (10 days postpartum) showed a very large increase in oxytocin mRNA, with smaller increases in vasopressin and dynorphin. No enkephalin or CRF (corticotrophin-releasing factor) changes were seen in lactating rats.

Lightman, S L; Young, W S · Animal Study

RPEP-00055 · 1987

Delta Sleep-Inducing Peptide Doesn't Meaningfully Improve Sleep in Insomniacs

Delta sleep-inducing peptide (DSIP) administered intravenously at 25 nmol/kg over four nights showed some improvements in sleep metrics in chronic insomniacs — including reduced awakenings, decreased waking time, and increased total sleep time — but these changes were not statistically significant compared to placebo. The only significant increases were in NREM sleep time and stage 2 sleep, but these differences already existed at baseline, undermining the finding. The authors concluded that DSIP's sleep-improving effects are of little clinical significance.

Monti, J M; Debellis, J; Alterwain, P; Pellejero, T; Monti, D · Randomized Controlled Trial

RPEP-00066 · 1988

Gut Hormone Cells Produce Dynorphin-Related Opioid Peptides Alongside Serotonin

Enterochromaffin (EC) cells are the most abundant hormone-producing cells in the gut. They were known to make serotonin. Whether they also make peptides was debated for years. Using antibodies against all three families of opioid peptide precursors, researchers tested gut tissue from dogs, guinea pigs, and humans. EC cells contained pro-dynorphin-derived peptides: dynorphin A and alpha-neo-endorphin. They did not contain pro-opiomelanocortin derivatives (like endorphin) or pro-enkephalin derivatives. Previous reports of enkephalin in EC cells were likely due to antibody cross-reactivity. The number and staining characteristics of opioid-positive EC cells varied considerably between species and between different segments of the gut, suggesting species-specific processing of the dynorphin precursor.

Cetin, Y · In Vitro

RPEP-00079 · 1988

How the Hypothalamus Uses Peptide Receptors to Control Hormones

Endogenous opioid peptides inhibit the release of both vasopressin and oxytocin from the posterior pituitary. They also affect anterior pituitary hormones through the hypothalamic portal blood system. Dynorphin mRNA co-exists in the same neurons as vasopressin. Stimuli that increase vasopressin secretion (like salt loading) also increase dynorphin mRNA accumulation. This parallel regulation strongly suggests dynorphin has a genuine role alongside vasopressin. Pro-enkephalin A mRNA co-exists with CRF in a different group of hypothalamic cells. Stresses that increase CRF mRNA also increase pro-enkephalin mRNA in the same area. The co-existence of opioid peptides with established hormones in the same cells, combined with their coordinated regulation, provides powerful evidence that opioids are genuine neuroendocrine regulators, not incidental bystanders.

Lightman, S L · Review

RPEP-00083 · 1988

Blocking Stress Hormone Receptors Changed Multiple Opioid and Reproductive Peptides

Alpha-helical CRF9-41 (a CRF receptor blocker) applied to hypothalamic slices in vitro caused beta-endorphin and met-enkephalin to drop significantly within 10 minutes. At the same time, LHRH (luteinizing hormone-releasing hormone) rose significantly. Dynorphin also decreased but the change was not statistically significant. When the antagonist was removed, the pattern reversed within 10 minutes: beta-endorphin, met-enkephalin, and dynorphin rose back up while LHRH fell back down. The same results were obtained in vivo using push-pull perfusion of the arcuate-median eminence region in anesthetized rats. This confirmed the in vitro findings in living animals.

Nikolarakis, K E; Almeida, O F; Sirinathsinghji, D J; Herz, A · Animal Study

RPEP-00084 · 1988

GABA Controls Reproductive Hormone Release Through Opioid Peptide Intermediaries

GABA at concentrations from 10^-8 to 10^-4 M caused a dose-dependent increase in GnRH release from rat hypothalamic slices. The GABA-A receptor agonist isoguvacine replicated this, while the GABA-B agonist baclofen had no effect. The GABA-A antagonist SR95103 blocked the GABA effect. Blockade of nerve conduction with tetrodotoxin abolished GABA's stimulatory effect, meaning it works through neural circuits, not directly on GnRH cells. Naloxone (opioid blocker) prevented GABA-induced GnRH release. The CRF antagonist also blocked it. CRF itself decreased GnRH release, and GABA could not reverse this. GABA stimulated the release of beta-endorphin, dynorphin, and met-enkephalin from the same tissue, connecting opioid peptide release to the control of reproduction.

Nikolarakis, K E; Loeffler, J P; Almeida, O F; Herz, A · In Vitro

RPEP-00088 · 1988

Cutting Any Peripheral Nerve Caused Brain-Wide Opioid Peptide Changes

Regardless of which nerve was cut (right or left sciatic, both sciatic, right brachial plexus, saphenous, or sural), the same brain-wide pattern emerged. Beta-endorphin decreased significantly in all brain areas except the striatum. Met-enkephalin increased in all brain areas and in the affected spinal cord segments. Substance P, somatostatin, and dynorphin were unaffected. The changes appeared within 24 hours of surgery and persisted for at least 4 months, indicating a long-lasting reorganization of the opioid system. There was no lateralization: unilateral nerve cuts produced bilateral brain changes. This means local nerve damage triggers a global brain response. Serotonergic drugs normalized beta-endorphin levels, suggesting the serotonin system mediates the opioid changes after nerve injury.

Panerai, A E; Sacerdote, P; Brini, A; Bianchi, M; Mantegazza, P · Animal Study

RPEP-00090 · 1988

Low-Dose Enkephalin Blocked Substance P Pain Without Producing Direct Pain Relief

Intrathecal (spinal cord) met-enkephalin at low doses markedly reduced the aversive behavior caused by intrathecal substance P. At these same low doses, met-enkephalin produced no measurable analgesia in the tail-flick pain test. Met-enkephalin needed much higher doses to produce general analgesia. Beta-endorphin and dynorphin-(1-17) were different. They blocked substance P-induced behavior and produced general analgesia at roughly the same doses. There was no separation between the two effects. This suggests met-enkephalin has a specific, preferential interaction with substance P-mediated pain signaling in the spinal cord, separate from its general painkilling effects.

Sakurada, T; Takahashi, K; Sakurada, S; Kisara, K; Folkesson, R; Terenius, L · Animal Study

RPEP-00093 · 1988

Male and Female Rat Brains Showed Different Enkephalin Patterns in a Reproductive Region

Three opioid peptide families showed distinct, non-overlapping distributions in the preoptic brain region. Beta-endorphin fibers were mainly in the periventricular nucleus. Dynorphin B fibers were more uniformly distributed with few cell bodies. Enkephalin (peptide E) had hundreds of cell bodies, concentrated in specific nuclei. The key sexual dimorphism: male rats had significantly more enkephalin cells in the anteroventral periventricular nucleus (AVPv) than females. This was despite the AVPv being physically larger in female rats. This sex difference was at least partially dependent on perinatal gonadal steroids. Early hormone exposure during the critical developmental window permanently organized the number of enkephalin cells, a process called organizational hormone effects. No sex difference was found in enkephalin cells in the anterodorsal preoptic nucleus, showing the dimorphism was region-specific, not a general property of enkephalin neurons.

Simerly, R B; McCall, L D; Watson, S J · Animal Study

RPEP-00118 · 1989

Enkephalin Nerve Fibers in the Prostate Decline With Age

Proenkephalin-derived peptide nerve fibers in human prostate were concentrated in the dorsolateral stroma and decreased in density with age. No prodynorphin or POMC-derived peptides were detected.

Jungblut, T; Aumüller, G; Malek, B; Melchior, H · Cross Sectional

RPEP-00146 · 1990

Dynorphin Injected Into the Brain Triggers Rapid Eating in Pigs

Full-length dynorphin A (1-17 or 1-13), leumorphin, and alpha-neo-endorphin induced rapid feeding in pigs. Shorter fragments were ineffective. Naloxone blocked all feeding effects.

Baldwin, B A; de la Riva, C; Ebenezer, I S · Animal Study

RPEP-00169 · 1990

A Hidden Brain Region Rich in Dynorphin, Substance P, and Zinc

The marginal division of the striatum has higher densities of zinc, dynorphin B-immunoreactive terminals, and substance P-immunoreactive terminals compared to the rest of the striatum.

Shu, S Y; McGinty, J F; Peterson, G M · Animal Study