Table 2.

Mechanisms of regulation for transporters in the intestine ^a

Transport proteins	Mechanism	Model system	Agonist/Causes	mRNA	Protein	Activity	Reference
BCRP	PXR	Duodenal biopsy (N = 12)	Rifampin (600 mg, 6 days)	↔	↔	ND	9
	PXR/CAR	Duodenal biopsy (N = 7)	Carbamazepine (600 mg, 14–18 days)	↑	↔	ND	9
	AhR	Caco‐2	Various AhR ligands	↑↑	↑	Apical transport of benzo[a]pyrene‐sulfate ↑	57
	DNA methylation, miRNA (indirect)	Colon carcinoma and adjacent “normal” tissue, colon (cancer) cell lines	DNA methyltransferase DNMT3b, siRNA miRNA‐203 (indirect)	↑↑	ND	↑↑	119
	miRNA and RNA binding protein	S1 and S1M1‐80, Caco‐2, HT‐29, and SW‐620 cells	miRNA‐519c	↓	↓↓	↓↓	60
	Localization	HT‐29 and Caco‐2	Uric acid (6 or 8 mg/dL)	↑	↑	↑	120
	Post‐translational	Colon biopsy from patients with chronic low‐grade inflammation–associated obesity	Loss of tyrosine phosphorylation (Janus kinase 3)	ND	↓↓	ND	121
MRP2	PXR	Duodenal biopsy (N = 16)	Rifampin (600 mg, 9 days)	↑	↑	ND	122
	PXR/CAR	Duodenal biopsy (N = 7)	Carbamazepine (600 mg, 14–18 days)	↑↑	↔	ND	9
OATP2B1	miRNA	Caco‐2 and HEK‐OATP2B1	miRNA‐24 mimic	Caco‐2: ↓↓ HEK‐OATP2B1: ↓	Caco‐2: ↓↓ HEK‐OATP2B1: ↓↓	Caco‐2: ↔ HEK‐OATP2B1: ↓	123
	Post‐translational, internalization	MDCKII‐OATP2B1 Caco‐2	Phorbol 12‐myristate 13‐acetate induced PKC activation	ND	↓	↓	51
	Localization	HEK‐OATP2B1 Caco‐2	Amiodarone Rutin Insulin (via Rab1)	ND	Plasma membrane↑ Total ↔	↑	124
P‐gp	PXR	Duodenal biopsy	Rifampin (600 mg, 10 days)	ND	↑↑	↑	125
	PXR	Duodenal biopsy	Rifampin (600 mg, 9 days)	↑	↑↑	AUC/Cmax of talinolol reduced by 35%/38%; ↑	126
	PXR/CAR	Duodenal biopsy (N = 7)	Carbamazepine (600 mg, 14–18 days)	↑↑	↔	ND	9
	miRNA	Intestinal tissue, luciferase reporter assay (HepG2)	miRNA‐27a‐3p and miRNA‐409‐3p	ND	↓	ND	22

↑, < 2‐fold increase; ↑↑, ≥ 2‐fold increase; ↓, < 2‐fold decrease; ↓↓, ≥ 2‐fold decrease; ↔, no change; ND, not determined.

^a AhR, aryl hydrocarbon receptor; AUC, area under the curve; BCRP, breast cancer resistance protein; Caco‐2, human colorectal adenocarcinoma cell; CAR, constitutive androstane receptor; C_max, maximum concentration; HEK, human embryonic kidney; HT‐29, human colonic adenocarcinoma cell line; MDCK, Madin‐Darby canine kidney; miRNA, microRNA; MRP, multidrug resistance‐associated protein; OATP, organic anion transporting polypeptide; P‐gp, P‐glycoprotein; PKC, protein kinase C; PXR, pregnane X receptor; siRNA, small interfering RNA; S1, human colon cancer cell line S1; S1M1‐80, mitoxantrone resistant S1 cell line derivative; SW‐620, human colonic adenocarcinoma cell line.