Our data shows that the presence of the polymorphisms at both positions 63 and 316 produce alterations in the CB2 receptor functions. Moreover, these findings strengthen the idea that the CB2 polymorphic receptors may contribute to the etiology of certain diseases.

The renal excretion of folic acid and methotrexate (MTX) was investigated in pentobarbital-anesthetized cynomolgus, rhesus, and AFrican green monkeys by standard clearance and stop-flow techniques. The renal clearance of folic acid was below inulin clearance at all plasma concentrations studied; the (U/P)folic/(U/P)In ratio increased from 0.26 at a concentration of 0.03 mM to a plateau value of 0.9 at concentrations above 0.2 mM, indicating net reabsorption by a saturable system. In stop-flow experiments, base-line (U/P)folic/(U/P)In ratios during free-flow periods were below 1.0, but increased by twofold in stop-flow samples derived from the proximal tubule, indicating net secretion during stopped flow. The stop-flow pattern of MTX excretion was similar, except the base-line flow pattern of MTX excretion was similar, except the base-line (U/P)MTX/(U/P)In ratio exceeded 1.0, indicating net secretion during both free-flow and stopped-flow periods. Secretion of both compounds was inhibited by p-aminohippuric acid and other organic acids but not by L-glutamic acid. It is concluded that folic acid is transported bidirectionally, while evidence was obtained only for secretion of MTX.

The stop-flow technique was used in dogs to determine the site of entry of urinary prostaglandins (PG) into tubular fluid. The proximal tubule was localized by the peak (U/PPAH)/(U/PIn) and the distal tubule and collecting duct by the peak U/PIn and the minimum (U/PNa)/(U/PIn). The peak of prostaglandin E (PGE) concentration was located 4.8+/-0.8 (SEM) ml distal to the proximal tubule and 4.6+/-0.8 (SEM) ml proximal to the distal nephron. At its peak, PGE was concentrated 6.3-fold over baseline, whereas inulin was concentrated 1.4-fold at its peak. The height of the PGE peak but not its location was increased by an i.v. infusion of angiotensin II at 20 ng/kg of body wt per min. Indomethacin abolished the PG peak. In a single experiment, prostaglandin F2alpha (PGF2alpha) exhibited an excretion pattern similar to PGE. These data indicate that the site of entry of PG into tubular fluid is most likely in the loop of Henle. This is consistent with the hypothesis that PG synthesized in the medulla can be transported to the cortex via tubular fluid. Whether PG in the tubular fluid can influence renal function remains to be determined.