Absorption of nicotinic acid and nicotinamide from rat small intestine in vitro

Sadoogh-Abasian, F.; Evered, David

doi:10.1016/0005-2736(80)90016-4

Cited by 27 publications

(8 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inability of previous studies to identify the existence of a high-affinity niacin uptake system is most probably due to the use of high working niacin concentrations (18,20). Previous studies have reported an apparent K m at 3.52 and 17.0 mM (4,14,18,20), which is rather high, considering that the luminal concentration of niacin was in the micromolar range. It is possible that the latter system (which is not specific for niacin but appears to be shared by other monocarboxylates; Refs.…”

Section: Discussionmentioning

confidence: 97%

“…Previous studies in laboratory animals have reported the mechanism to function either via simple diffusion of the undissociated form of nicotinic acid (according to the pH partition hypothesis and assisted by acid microclimate at the luminal surface of the intestine) (3) or via a carrier-mediated mechanism (4,14,18,20). The latter studies, however, reported an apparent Michaelis-Menten constant (K m ) for the carrier-mediated process from 3.52 to 17.0 mM.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Mechanism and regulation of human intestinal niacin uptake

Nabokina¹,

Kashyap²,

Said³

2005

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

The mechanism of uptake of dietary niacin (nicotinic acid) by intestinal epithelial cells is not well understood, and nothing is known about regulation of the uptake process. In this investigation, we used human-derived intestinal epithelial Caco-2 cells and purified intestinal brush-border membrane vesicles (BBMVs) isolated from human organ donors to assess niacin uptake. Our findings show niacin uptake by Caco-2 cells to be 1) temperature and energy dependent; 2) Na ϩ independent, but highly dependent on extracellular acidic pH; 3) saturable as a function of concentration, with an apparent K m of 0.53 Ϯ 0.08 M; 4) severely inhibited by the membrane-impermeable sulfhydryl group of reagents; and 5) highly specific for niacin but not affected by monocarboxylic acids. A marked trans stimulation in [ 3 H]niacin efflux from preloaded Caco-2 cells by unlabeled niacin in the incubation buffer was also observed. These findings suggest the involvement of a specialized, pH-dependent, carrier-mediated mechanism for human intestinal niacin uptake. This suggestion was confirmed in studies with native human intestinal BBMVs. We also examined possible regulation of niacin uptake by Caco-2 cells via specific intracellular regulatory pathways. The results show that while the PKA-, PKC-, and Ca 2ϩ / calmodulin-mediated regulatory pathways play no role in regulating niacin uptake, a role for a protein tyrosine kinase (PTK)-mediated pathway is apparent. The results of these studies show for the first time the existence of a specialized, acidic pH-dependent, carriermediated system of niacin uptake by human intestinal epithelial cells that operates at the micromolar (physiological) range of niacin. The results also suggest the possible involvement of a PTK-mediated pathway in the regulation of niacin uptake. intestinal transport; transport mechanism; transport regulation NIACIN (NICOTINIC ACID), a water-soluble vitamin, acts as a precursor to the synthesis of the coenzymes NAD and NADP, which are involved in important reactions that maintain the redox state of cells (e.g., glycolysis, pentose phosphate shunt) (8, 9). In pharmacological doses, niacin reduces plasma triglycerides, cholesterol, and atherogenic apolipoprotein B (apoB)-containing lipoproteins and increases antiatherogenic apoA-I-containing high-density lipoprotein level, thus preventing atherosclerotic cardiovascular disease (10, 11). Humans have access to niacin from endogenous and exogenous sources (1, 9). The endogenous source of niacin is provided via the metabolic conversion of amino acid tryptophan to niacin. The exogenous source is provided through the diet by absorption in the intestine.The mechanism involved in the intestinal absorption of dietary niacin, and its regulation, is not well understood. Previous studies in laboratory animals have reported the mechanism to function either via simple diffusion of the undissociated form of nicotinic acid (according to the pH partition hypothesis and assisted by acid microclimate at the luminal surface of the intestine) ...

show abstract

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Mechanism and regulation of human intestinal niacin uptake

Nabokina¹,

Kashyap²,

Said³

2005

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

“…It is an essential dietary constituent and is readily absorbed from the intestinal tract (Bechgaard and Jespersen, 1977; Sadoogh-Abasian and Evered, 1980). Since the whole body autoradiogram after intravenous administration of [ 3 H]-nicotinic acid in mice shows the presence of radioactivity in the eye as early as 5 min after injection (Carlson and Hanngren, 1964), it is conceivable that nicotinic acid is supplied to the retina from the circulating blood after its absorption in intestinal tract.…”

Section: Introductionmentioning

confidence: 99%

Retinal transfer of nicotinate by H+-monocarboxylate transporter at the inner blood-retinal barrier

Tachikawa

Murakami

Martin

et al. 2011

Microvascular Research

View full text Add to dashboard Cite

Nicotinic acid is a constituent of the coenzymes NAD and NADP. It also serves as an agonist for the G-protein-coupled receptor GPR109A. Nicotinic acid is widely used at high doses as a lipid-lowering drug, which is associated with an ocular side effect known as niacin maculopathy. Here we investigated the mechanism by which nicotinate is transferred into retina across the inner blood-retinal barrier (BRB). In vivo the blood-to-retina transport of [3H]-nicotinate was studied using the carotid artery injection technique. The characteristics of nicotinate transport at the inner BRB were examined in a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2), an in vitro model of inner BRB. The expression of transporters in TR-iBRB2 cells was determined by reverse transcription-polymerase chain reaction. In vivo [3H]-nicotinate uptake by the retina was 5.4-fold greater than that of [14C]-sucrose, a BRB impermeable vascular space marker. Excess amounts of unlabeled nicotinate and salicylate significantly decreased the in vivo retinal uptake of [3H]-nicotinate. [3H]-Nicotinate was taken up by TR-iBRB2 cells via an H+-dependent saturable process with a Michaelis constant of ~7 mM. Na+ had minimal effect on the uptake. The H+-dependent uptake was significantly inhibited by endogenous monocarboxylates such as lactate and puruvate, and monocarboxylic drugs such as valproate, salicylate, and ibuprofen. These characteristics are consistent with those of H+-coupled monocarboxylate transporters (MCTs). MCT1, MCT2, and MCT4 mRNAs were expressed in TR-iBRB2 cells. The Na+-dependent monocarboxylate transporters SMCT1 and SMCT2 were not expressed in these cells. In conclusion, transfer of nicotinate from blood to retina across the inner BRB occurs primarily via H+-coupled monocarbxylate transporters.

show abstract

“…This system was found to function at the physiological (micromolar) concentration range of the vitamin and is specific for nicotinic acid. In addition to providing a challenge to the previous belief that the intestinal nicotinic acid uptake process involves a nonspecific low-affinity uptake system (7,22,28,30), these findings have also raised the possibility that a similar uptake process may function in other cell types if the proper conditions are used to study the vitamin uptake event. Our aim in the present study was, therefore, to to test this possibility in human hepatocytes using both human-derived liver HepG2 cells and human primary hepatocytes as models.…”

mentioning

confidence: 98%

“…A low-affinity and nonspecific nicotinic acid membrane transport system(s) has been proposed to function in a number of tissues, including the intestine (2, 6, 7, 22, 28 -30), but the importance of such a system(s) in transporting physiological concentrations of the vitamin is not clear. A recent study (22) has reported the existence of a high-affinity system for nicotinic acid uptake in human intestinal epithelial cells. This system was found to function at the physiological (micromolar) concentration range of the vitamin and is specific for nicotinic acid.…”

mentioning

confidence: 99%

Mechanism of nicotinic acid transport in human liver cells: experiments with HepG2 cells and primary hepatocytes

Said¹,

Nabokina²,

Balamurugan³

et al. 2007

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

This study reports on the functional expression of a specific, high-affinity carrier-mediated mechanism for the transport of niacin (nicotinic acid) in human liver cells. Both human-derived liver HepG2 cells and human primary hepatocytes were used as models in these investigations. The initial rate of transport of nicotinic acid into HepG2 cells was found to be acidic pH, temperature, and energy dependent; it was, however, Na(+) independent in nature. Evidence for the existence of a carrier-mediated system that is specific for [(3)H]nicotinic acid transport was found and included the following: 1) saturability as a function of concentration with an apparent K(m) of 0.73 +/- 0.16 microM and V(max) of 25.02 +/- 1.45 pmol.mg protein(-1).3 min(-1), 2) cis-inhibition by unlabeled nicotinic acid and nicotinamide but not by unrelated organic anions (lactate, acetate, butyrate, succinate, citrate, and valproate), and 3) trans-stimulation of [(3)H]nicotinic acid efflux by unlabeled nicotinic acid. Transport of the vitamin into human primary hepatocytes occurs similarly via an acidic pH-dependent and specific carrier-mediated process. Inhibitors of the Ca(2+)-calmodulin-mediated pathway (but not modulators of the PKC-, PKA-, and protein tyrosine kinase-mediated pathways) inhibited nicotinic acid transport into both HepG2 cells and human primary hepatocytes. Maintenance of HepG2 cells (for 48 h) in growth medium oversupplemented with nicotinic acid (or nicotinamide) did not affect the subsequent transport of [(3)H]nicotinic acid into HepG2 cells. These results show, for the first time, the existence of a specific and regulated membrane carrier-mediated system for nicotinic acid transport in human liver cells.

show abstract

Absorption of nicotinic acid and nicotinamide from rat small intestine in vitro

Cited by 27 publications

References 13 publications

Mechanism and regulation of human intestinal niacin uptake

Mechanism and regulation of human intestinal niacin uptake

Retinal transfer of nicotinate by H+-monocarboxylate transporter at the inner blood-retinal barrier

Mechanism of nicotinic acid transport in human liver cells: experiments with HepG2 cells and primary hepatocytes

Contact Info

Product

Resources

About