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PubMed1980

Origin of glycerylphosphorylcholine, inositol, N-acetylaminosugar, and prostaglandins in human seminal plasma and their effects on sperm metabolism.

The origin of glycerylphosphorylcholine (GPC), N-acetylaminosugar, inositol, and prostaglandins in human seminal plasma was investigated by correlating the concentration of these components in split ejaculates with known marker constituents. Fructose and acid phosphatase were selected as markers of the secretory activity of the seminal vesicles and prostate gland, respectively, and spermatozoa indicated epididymal origin. The concentration of fructose was lowest in the first fraction of the semen and increased to a maximum in the final portion. Prostaglandins E and F and N-acetylaminosugar values closely followed this pattern, indicating that these components originate in the seminal vesicles. The concentration of spermatozoa was high in the first two fractions, decreasing to a minimum in the final fraction. The distribution of GPC was similar to that of the spermatozoa, indicating that the epididymis secretes this compound. Inositol levels were similar in all fractions, indicating that it is probably present in epididymal, vesicular, and prostatic fluid. Human spermatozoa were unable to utilize N-acetylglucosamine or inositol. High concentrations of some prostaglandins (100 micrograms/ml of PGF1 alpha, 15S 15 met. F2 alpha, PGA1, and PGA2) depressed the endogenous oxygen uptake of human spermatozoa.

Acetylglucosamine↗
PubMed1992

A comparative study of free plasma choline levels following intramuscular administration of L-alpha-glycerylphosphorylcholine and citicoline in normal volunteers.

L-alpha-glycerylphosphorylcholine (alpha-GPC) is a recently developed cognitive enhancer whose mode of action is considered to involve the release of free choline, which is then utilized for acetylcholine and phosphatidylcholine biosynthesis in the brain. The purpose of this study was to evaluate the profile of free plasma choline levels following a single i.m. dose of alpha-GPC in 12 normal volunteers. Citicoline (CTC), which also acts as a choline precursor, was included for comparison purposes. Each subject was studied on three randomized occasions, (i) in a control day in the absence of drug administration (to evaluate the plasma level profile of endogenous choline), (ii) after i.m. alpha-GPC (1,000 mg) and (iii) after i.m. CTC (1,000 mg) respectively, with a wash-out period of at least 1-week between sessions. Blood samples for plasma choline HPLC determinations were collected at regular intervals over a 6 h period. In the control session, plasma choline levels remained stable during the sampling period. The administration of alpha-GPC was associated with a rapid rise in plasma choline, peak levels being usually observed at the first (0.25 h) or second (0.5 h) sampling time after the injection. Thereafter, the concentration of choline declined gradually and returned to near baseline values at the end of the observation period. After the administration of CTC, plasma choline levels showed a similar time course but were considerably lower than those observed after the administration of alpha-GPC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Glycerylphosphorylcholine levels in the coagulational groups of human ejaculates.

The amount of coagulum present in fresh ejaculates of men (among infertile couple) varied directly with the levels of seminal glycerylphosphorylcholine (GPC; P less than 0.001), which is secreted predominantly by the epididymis. GPC concentrations (mg/ml) of the normally and poorly coagulating ejaculates revealed close similarities with those of the presumably fertile (1.72 +/- 0.10) and infertile semen (1.13 +/- 0.08) respectively. The study suggests that the degree of coagulation of human ejaculates may be correlated with epididymal function.

Adult↗
PubMed1986

Changes in the interaction between CNS cholinergic and dopaminergic neurons induced by L-alpha-glycerylphosphorylcholine, a cholinomimetic drug.

The present study investigates the cholinomimetic properties of the drug L-alpha-glycerylphosphorylcholine (alpha-GPC) at CNS level. Experiments using tritium labelled alpha-GPC indicate that the drug reaches the brain after i.p. and per os administration. In order to study the cholinomimetic properties of this drug an indirect functional index of cholinergic activation was used. In fact cholinergic agonists induce an activation of striatal dopaminergic output. alpha-GPC both i.p. and per os administered increased striatal dihydroxyphenylacetic acid (DOPAC) content. In addition, the in vitro K+ stimulated dopamine release was increased in rats treated in vivo with alpha-GPC. Since alpha-GPC has a weak displacing activity in QNB binding, the in vivo cholinergic activity might be due to the fact that this drug may increase the availability of choline for acetylcholine synthesis leading to increased acetylcholine production. This activity may be useful in those situations such as aging in which cholinergic activity is deficient.

Animals↗
PubMed1991

Effect of a new cognition enhancer, alpha-glycerylphosphorylcholine, on scopolamine-induced amnesia and brain acetylcholine.

The present study investigates the effect of the administration of alpha-glycerylphosphorylcholine (alpha-GPC) on scopolamine-induced amnesia and on brain acetylcholine (ACh) levels and release in rats. The results indicate that alpha-GPC, when administered orally, reverses the amnesia caused by scopolamine in passive avoidance. The peak effect is observed using 600 mg/kg IG, 5 h before training. The effect of the drug is long lasting (up 30 h) in accordance with its pharmacokinetic characteristics. Since, alpha-GPC administered IG is cleaved within the gut mucosal cells to glycerophosphate and free choline, it is tempting to speculate that this drug acts by increasing the ACh precursor pool. This view is supported also by the observation that alpha-GPC partially counteracts the decrease of brain ACh levels elicited by scopolamine administration. The effect is observed in the hippocampus and cortex, but not in the striatum. Moreover, in ex vivo experiments, alpha-GPC is able to increase the amount of ACh released by rat hippocampus slices following potassium stimulation.

Acetylcholine↗
PubMed1992

Glycerylphosphorylcholine (GPC) diesterase related alterations in the oxygen consumption profile of rat spermatozoa in differing functional states.

The functional interaction of the estrogen-induced uterine enzyme glycerylphosphorylcholine (GPC) diesterase with epididymal rat sperm before and after incubation under capacitating conditions was investigated indirectly, by measuring the glycerol phosphate (GP) released on enzymatic hydrolysis of GPC and using oxygen consumption as a measure of oxidative phosphorylation by the sperm. Freshly released, washed sperm metabolized GP but not GPC. Utilization of GP was found to be inhibited by 2 microM oligomycin but was enhanced dose-dependently in the presence of the uncoupling agent, 2,4-dinitrophenol, indicating that the process was essentially similar to that occurring in somatic mitochondria in that it involved electron transport via ubiquinone and the cytochrome system and was coupled to ATP synthesis. However, on incubation of sperm under conditions supporting capacitation, which led to a striking increase in oxygen consumption, the presence of GP decreased oxygen uptake significantly, in a manner similar to that occurring in the presence of the glycolysable substrate, glucose. The implications of these GPC diesterase-induced metabolic alterations in sperm function are discussed.

Animals↗
PubMed1991

Purification and characterization of rat uterine glycerylphosphorylcholine diesterase and its tissue-specific induction by 17 beta-estradiol.

The rat uterine enzyme glycerylphosphorylcholine (GPC) diesterase found in the proestrous secretions was purified and characterized biochemically with respect to its subunit mol wt, native size, pI, and amino acid and carbohydrate composition. The 30-kDa protein was assessed to have a native mol wt of 105 kDa, as determined by analytical gel filtration. It had a basic pI with an unusually high carbohydrate/protein ratio (0.83:1). The estrogen inducibility of the protein was identified by its de novo synthesis in vitro after in vivo 17 beta-estradiol administration. For this experiment, uteri from estradiol-treated immature rats were incubated in the presence of [14C]glucosamine, and the 14C-labeled total glycoconjugates were then subjected to the enzyme purification procedure. The peak enzyme fraction was observed to correspond to one of the 14C-labeled protein peaks in the elution profile of the glycoconjugates. Assay of GPC diesterase activity showed significant enhancement only in the uterus, not in other organ systems, after in vivo estradiol treatment, and this hormone-stimulated increase was inhibited by nafoxidine, a potent estrogen antagonist. The enzyme activity profile of the three main separated uterine cellular types showed that the enzyme was secreted by epithelial cells. No antigenic homology of the enzyme was observed with GPC diesterase from nonmammalian sources. The results suggested that GPC diesterase was one of the estrogen-regulated proteins of the preovulatory uterine fluid of rats, and the availability of a purified preparation of the enzyme could serve as a useful tool to study the mechanism of estrogen action.

Amino Acids↗
PubMedDate not supplied

Absorption, tissue distribution and excretion of radiolabelled compounds in rats after administration of [14C]-L-alpha-glycerylphosphorylcholine.

The kinetics and metabolism of L-alpha-glycerylphosphoryl-choline (alpha-GPC) were investigated in male and female rats after i.v. (10 mg/kg) and oral doses (100-300 mg/kg). alpha-GPC was labelled with [14C]-glycerol ([14G]-GPC) or [14C]-choline ([14C]-GPC). Different kinetic and metabolic profiles were observed after i.v. and oral administration. It is assumed that alpha-GPC is hydrolyzed by phosphodiesterases in the gut mucosa. The different labelled metabolites have different kinetic properties of absorption, distribution and clearance, leading to different blood concentration-time curves of total radioactivity. Both labelled compounds gave a wide distribution of radioactivity, particularly concentrated in the liver, kidney, lung and spleen compared to blood. Brain concentrations of [14C]-GPC were comparable to ([14G]-GPC) or lower than ([14C]-GPC) total blood radioactivity. The metabolite profile in the perfused brain showed a small amount of choline and two unknown metabolites, probably the same as in blood. In addition, choline was incorporated into brain phospholipids in increasing amounts within 24 h of dosing. In all cases renal and fecal excretion of radioactivity was low and comparable for [14G]-GPC and [14C]-GPC. Mostly the administered radioactivity was exhaled as 14CO2, this degradation being faster and more pronounced for the glycerol-labelled metabolites than for the choline-labelled metabolites for both routes of administration. In all cases the results were the same for male and female rats.

Absorption↗