Sex Difference in the Transport of p-Aminohippurate by the Rat Kidney1

Kleinman, Leonard I.; Loewenstein, Matthew S.; Goldstein, Léon

doi:10.1210/endo-78-2-403

Cited by 37 publications

(31 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gonadectomy of male rats reduced kidney PAH transport, which was restored by testosterone administration (Kleinman et al, 1966;Bräunlich et al, 1993). However, PAH transport was not affected by ovariectomy of female rats or estradiol administration to male rats (Kleinman et al, 1966;Bräunlich et al, 1993). Thus, estrogens did not influence the organic anion transport processes of the kidney.…”

Section: Discussionmentioning

confidence: 87%

“…Male rat kidneys reportedly accumulate PAH at a greater rate than female rat kidneys (Huang and McIntosh, 1955;Kleinman et al, 1966;Bowman and Hook, 1972). Gonadectomy of male rats reduced kidney PAH transport, which was restored by testosterone administration (Kleinman et al, 1966;Bräunlich et al, 1993).…”

Section: Discussionmentioning

confidence: 94%

“…Select transport proteins in kidney, including organic anion transporting polypeptide 1 (oatp1), organic cation transporter 2, and organic anion transporters (Oats) also exhibit gender-divergent expression (Lu et al, 1996;Urakami et al, 1999;Kobayashi et al, 2002;Buist et al, 2002;Slitt et al, 2002). Moreover, male rat kidneys transport para-aminohippurate (PAH), an anion commonly used to study active transport in kidney, at greater rates than female rat kidneys, both in vivo and in vitro (Kleinman et al, 1966). Kleinman et al (1966) and Bräunlich et al (1993), respectively, determined that testosterone elevated PAH transport by male kidney, and estrogen had no role in gender-divergent PAH transport.…”

mentioning

confidence: 99%

“…Moreover, male rat kidneys transport para-aminohippurate (PAH), an anion commonly used to study active transport in kidney, at greater rates than female rat kidneys, both in vivo and in vitro (Kleinman et al, 1966). Kleinman et al (1966) and Bräunlich et al (1993), respectively, determined that testosterone elevated PAH transport by male kidney, and estrogen had no role in gender-divergent PAH transport. Testosterone was also shown to increase expression of oatp1 in kidney (Lu et al, 1996).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Endocrine Regulation of Rat Organic Anion Transporters

Buist¹,

Cherrington²,

Klaassen³

2003

Drug Metab Dispos

View full text Add to dashboard Cite

This article is available online at http://dmd.aspetjournals.org ABSTRACT:Messenger RNA levels of rat organic anion transporter 1 (Oat1; Slc22a6) and Oat2 (Slc22a7) in kidney and Oat3 (Slc22a8) in liver are gender-predominant. Oat1 and Oat3 are male-predominant, whereas Oat2 is female-predominant. Gonadectomized and hypophysectomized (HX) rats were studied to determine whether sex steroids and/or growth hormone (GH) are responsible for these gender-divergent patterns. GH was administered to HX rats by two daily injections (simulating male secretion) or continuous infusion (simulating female secretion). Oat1 mRNA levels, normally higher in male than female kidney, were lowered by gonadectomy and HX in male rats, but not in females. Additionally, GH injections or infusion did not alter Oat1 levels in HX rats. Oat2 mRNA levels, typically much higher in female than in male kidney, were unaffected by gonadectomy. However, HX dramatically decreased Oat2 in female kidney without altering male levels. GH administered by continuous infusion increased Oat2 in kidneys of both HX male and female rats, whereas injections had no affect. Gonadectomy reduced Oat3 mRNA levels in male livers without affecting levels in female livers. In contrast, HX decreased male and elevated female Oat3 mRNA. GH injections did not significantly change Oat3 mRNA levels in HX rats, but infusion decreased Oat3 mRNA in liver. In conclusion, androgens, but not GH, are responsible for the Oat1 mRNA gender difference in kidney; the female GH secretion pattern is responsible for the Oat2 mRNA gender difference in kidney; and both androgens and the female GH secretion pattern are responsible for the Oat3 mRNA gender difference in liver.Metabolism and excretion both determine elimination of endogenous and exogenous compounds. Liver is the primary site of metabolism, and liver and kidney are important organs in the process of excretion. Increasing or decreasing metabolism or excretion can lead to a respective decrease or increase of xenobiotic half-life, thus altering disposition. Expression of phase I [e.g., cytochromes P450 (P450s 1 )] and phase II enzymes [e.g., glucuronosyltransferases and sulfotransferases (STs)] is critical to metabolic processes, whereas transport proteins are vital for excretion. Interestingly, some enzymes and transporters are expressed in a gender-specific manner.

show abstract

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Endocrine Regulation of Rat Organic Anion Transporters

Buist¹,

Cherrington²,

Klaassen³

2003

Drug Metab Dispos

View full text Add to dashboard Cite

show abstract

“…Drugs must traverse across biological membranes via simple diffusion or physiological transporters to produce therapeutic efficacy (Levy, 1998). Gender-associated differences in transport processes for endogenous and exogenous substrates have been reported in various organs of the body, including kidney, liver, intestine, and brain, for rats, mice, and humans (Kleinman et al, 1966;Orzes et al, 1985;Anton et al, 1986;Morissette et al, 1990;UhlandSmith and DeLuca, 1993;Sibug et al, 1996). Table 1 summarizes the gender-associated differences in transport activities in humans, evaluated predominantly in clearance studies, whereas Table 2 summarizes the literature information regarding gender differences in transporter mRNA and/or protein expression in tissues.…”

Section: Introductionmentioning

confidence: 99%

Gender Differences in the Membrane Transport of Endogenous and Exogenous Compounds

2003

View full text Add to dashboard Cite

Pharmacokinetic Disposition of Loracarbef in Healthy Young Men and Women at Steady State

Sitar

Hoban

Aoki

1994

The Journal of Clinical Pharma

View full text Add to dashboard Cite

The pharmacokinetic disposition of 200- and 400-mg doses of a novel carbacephem, loracarbef, was determined over a dose interval on day 8, after ingestion of drug doses twice daily for 7 days, in 20 young, healthy volunteers of both genders. Drug was analyzed in plasma, urine, saliva, vaginal secretions, and fecal filtrate. Peak plasma concentration was proportional to dose for both men (4.0 +/- 1.3 and 8.8 +/- 3.4 mg/L) and women (8.0 +/- 5.6 and 15.3 +/- 3.3 mg/L), and the observed time to peak increased from 1 to 2 hours with the increased dose. Apparent volume of distribution was greater in men than women (0.385 +/- 0.114 versus 0.270 +/- 0.075 L/kg; P < .03). The drug was virtually quantitatively excreted unchanged in urine, and its renal clearance exceeded creatinine clearance in all subjects. Renal loracarbef clearance correlated with neither weight-corrected dose nor creatinine clearance in these healthy subjects. There was no evidence for drug accumulation in the body with chronic ingestion. Loracarbef was detected in the fecal filtrate of seven volunteers, but did not account for more than 7% of the daily dose. Loracarbef was detected in vaginal secretions of two of five volunteers who ingested the 400-mg dose. No drug was detected in saliva obtained just before dose ingestion. These data are consistent with complete bioavailability for an oral beta-lactam antibiotic drug that is virtually completely eliminated unchanged by the kidney.

show abstract

Sex Difference in the Transport of p-Aminohippurate by the Rat Kidney1

Cited by 37 publications

References 0 publications

Endocrine Regulation of Rat Organic Anion Transporters

Endocrine Regulation of Rat Organic Anion Transporters

Gender Differences in the Membrane Transport of Endogenous and Exogenous Compounds

Pharmacokinetic Disposition of Loracarbef in Healthy Young Men and Women at Steady State

Contact Info

Product

Resources

About