[Leu5]-Enkephalin

BACKGROUND: ;Endogenous opioids, enkephalins, are known to increase with acute kidney injury. Since the mature pentapeptides are unstable, we evaluated the performance of an assay that measures proenkephalin 119-159 (PENK), a stable peptide formed concomitantly with mature enkephalins.;METHODS: ;PENK assay performance was evaluated on two microtiterplate/chemiluminescence sandwich immunoassay formats that required 18 or 1 h incubation times. PENK concentration was measured in plasma from healthy individuals to establish a reference interval and in patients with varied levels of kidney function and comorbidities to assess the association with measured glomerular filtration rate (mGFR) using iothalamate clearance.;RESULTS: ;Assay performance characteristics in plasma were similar between the assay formats. Limit of quantitation was 26.0 pmol/L (CV = 20%) for the 1 h assay and 17.3 pmol/L (CV = 3%) for the 18 h assay. Measurable ranges were 26-1540 pmol/L (1 h assay) and 18-2300 pmol/L (18 h assay). PENK concentrations are stable in plasma stored ambient to 10 days, refrigerated to at least 15 days, and frozen to at least 90 days. Results were comparable in paired SST serum and EDTA plasma.

The aim of this investigation was to study the effects of the peptides bombesin, calcitonin, and enkephalin on net jejunal water and electrolyte fluxes using the triple-lumen gut perfusion technique in conscious dogs. Intestinal transport was measured during intravenous infusions of bombesin (1 microgram/kg/hr, 8 studies), or calcitonin (3 micrograms/kg/hr, 5 studies), or methionine enkephalin (20 micrograms/kg/hr, 6 studies); each dog was used as its own control with infusion of 150 mmol/liter NaCl preceding and succeeding each peptide infusion. Net water absorption was reduced from a control value of 17 +/- 4.18 to 7 +/- 1.79 microliter/cm/min by bombesin (P less than 0.05) and increased from a control value of 15 +/- 3.95 to 29 +/- 5.58 microliters/cm/min by enkephalin (P less than 0.05). Bombesin reduced net sodium and chloride absorption, while enkephalin increased net absorption of sodium and bicarbonate. Calcitonin did not have any detectable effect in the dose used in this study in dogs. We conclude that bombesin and enkephalin can effect the transport of water and electrolytes in the canine jejunum.

Medium spiny neurons (MSNs) constitute 95% of neurons in the dorsal striatum subdivided into direct (striatonigral) and indirect (striatopallidal) pathways. Whereas D1 and D2 receptors and several neuropeptides, including dynorphin and enkephalin, are differentially expressed in these neurons, 5-hydroxytryptamine 6 receptors (5-HT6) are expressed in both pathways. Previous results demonstrate that concurrent 5-HT6 receptor overexpression in MSNs of both pathways in the dorsomedial striatum (DMS) interferes with instrumental learning and that 5-HT6 overexpression in the dorsolateral striatum (DLS) relieves rats from inflexible habitual behaviors. We hypothesized that 5-HT6 receptor-mediated co-activation of both pathways interferes with the differential activation/inhibition of direct/indirect pathways by dopamine. To test this idea, we cloned novel viral vectors to selectively overexpress 5-HT6 receptors in direct or indirect pathway MSNs to deconstruct their role in modulating instrumental learning and habitual responding. We found that increasing 5-HT6 receptor expression in either direct or indirect pathway MSNs of the posterior DMS selectively enhanced or impaired initial acquisition of a discrete instrumental learning task respectively, though all rats were ultimately able to learn the task.