Abstract
Cannabis is the most commonly used illicit drug worldwide. Cannabis users also appear to use other psychoactive drugs more frequently than noncannabis users. Here, Δ9- tetrahydrocannabinol (THC) and diazepam binding to human serum albumin (HSA) and HSA-heme is reported. THC binds to two different binding sites of HSA (Kd1 ≤ 10-7 M and Kd2 = 10-3 M) without affecting diazepam binding (Kd = 1.2 × 10-5 M). THC binding to the high-affinity site accounts for the low free fraction of the drug in plasma. Moreover, THC increases the affinity of heme for HSA. Accordingly, the affinity of THC for HSA-heme is higher than that for HSA. THC could bind to FA2 and FA7 sites, as substantiated by docking simulations; nevertheless, the observed allosteric effect(s) suggests that the primary binding site of THC is the FA2 cleft that positively modulates heme affinity. Possibly, the HSA conformational transition(s) induced by THC binding could account for drug delivery to the liver through receptor-mediated endocytosis.
| Original language | English |
|---|---|
| Pages (from-to) | 446-451 |
| Number of pages | 6 |
| Journal | IUBMB Life |
| Volume | 63 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2011 |
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Keywords
- Δ9-tetrahydrocannabinol binding
- conformational transition(s)
- diazepam binding
- human serum albumin
- pharmacokinetics
- poly-drug use
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Clinical Biochemistry
- Molecular Biology
- Genetics
Cite this
Binding of Δ9-tetrahydrocannabinol and diazepam to human serum albumin. / Fanali, Gabriella; Cao, Yu; Ascenzi, Paolo; Trezza, Viviana; Rubino, Tiziana; Parolaro, Daniela; Fasano, Mauro.
In: IUBMB Life, Vol. 63, No. 6, 06.2011, p. 446-451.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Binding of Δ9-tetrahydrocannabinol and diazepam to human serum albumin
AU - Fanali, Gabriella
AU - Cao, Yu
AU - Ascenzi, Paolo
AU - Trezza, Viviana
AU - Rubino, Tiziana
AU - Parolaro, Daniela
AU - Fasano, Mauro
PY - 2011/6
Y1 - 2011/6
N2 - Cannabis is the most commonly used illicit drug worldwide. Cannabis users also appear to use other psychoactive drugs more frequently than noncannabis users. Here, Δ9- tetrahydrocannabinol (THC) and diazepam binding to human serum albumin (HSA) and HSA-heme is reported. THC binds to two different binding sites of HSA (Kd1 ≤ 10-7 M and Kd2 = 10-3 M) without affecting diazepam binding (Kd = 1.2 × 10-5 M). THC binding to the high-affinity site accounts for the low free fraction of the drug in plasma. Moreover, THC increases the affinity of heme for HSA. Accordingly, the affinity of THC for HSA-heme is higher than that for HSA. THC could bind to FA2 and FA7 sites, as substantiated by docking simulations; nevertheless, the observed allosteric effect(s) suggests that the primary binding site of THC is the FA2 cleft that positively modulates heme affinity. Possibly, the HSA conformational transition(s) induced by THC binding could account for drug delivery to the liver through receptor-mediated endocytosis.
AB - Cannabis is the most commonly used illicit drug worldwide. Cannabis users also appear to use other psychoactive drugs more frequently than noncannabis users. Here, Δ9- tetrahydrocannabinol (THC) and diazepam binding to human serum albumin (HSA) and HSA-heme is reported. THC binds to two different binding sites of HSA (Kd1 ≤ 10-7 M and Kd2 = 10-3 M) without affecting diazepam binding (Kd = 1.2 × 10-5 M). THC binding to the high-affinity site accounts for the low free fraction of the drug in plasma. Moreover, THC increases the affinity of heme for HSA. Accordingly, the affinity of THC for HSA-heme is higher than that for HSA. THC could bind to FA2 and FA7 sites, as substantiated by docking simulations; nevertheless, the observed allosteric effect(s) suggests that the primary binding site of THC is the FA2 cleft that positively modulates heme affinity. Possibly, the HSA conformational transition(s) induced by THC binding could account for drug delivery to the liver through receptor-mediated endocytosis.
KW - Δ9-tetrahydrocannabinol binding
KW - conformational transition(s)
KW - diazepam binding
KW - human serum albumin
KW - pharmacokinetics
KW - poly-drug use
UR - http://www.scopus.com/inward/record.url?scp=79959613725&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959613725&partnerID=8YFLogxK
U2 - 10.1002/iub.466
DO - 10.1002/iub.466
M3 - Article
C2 - 21557446
AN - SCOPUS:79959613725
VL - 63
SP - 446
EP - 451
JO - IUBMB Life
JF - IUBMB Life
SN - 1521-6543
IS - 6
ER -