The effect of recombinant insulin-like growth factor I (IGF-I) on Pi uptake by a rat osteoblast-like cell line (UMR-106-01) in culture was investigated. IGF-I (10(-6)-10(-8) M) caused a dose-related stimulation of Na(+)-Pi cotransport. A 30-70% increase in Na(+)-dependent Pi uptake over control values was observed after 1- to 5-h exposure of these cells to 10(-7) M IGF-I. The increase was detected within 45 min, in contrast to the slower action of insulin. This effect of IGF-I was specific for Na(+)-Pi uptake, because Na(+)-independent Pi uptake and Na(+)-alanine cotransport were unaffected by IGF-I. A reversal of IGF-I induced stimulation of Na(+)-Pi cotransport was observed within 1 h of removal of the hormone. Kinetic analysis of the IGF-I effect indicates a significant change only in the apparent maximum velocity (Vmax) of Na(+)-Pi cotransport. The Vmax was 5.22 +/- 0.47 vs. 3.33 +/- 0.45 nmol Pi.mg protein-1.10 min-1 in confluent monolayers exposed to 10(-7) M IGF-I and vehicle alone, respectively, for 3 h (P less than 0.05, group t test). Blocking de novo protein synthesis with cycloheximide had no effect on this stimulatory effect of IGF-I. These observations indicate that IGF-I specifically stimulates Pi uptake in osteoblastic cells. The effect is characterized by an increase in Vmax and is not dependent on de novo protein synthesis. The mechanism remains to be determined.

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The possible role of adenosine 3',5'-cyclic monophosphate (cAMP) in the mechanism of the acute inhibitory effects of nicotinamide and analogues on brush-border membrane (BBM) phosphate transport was investigated. Compared with basal values, cAMP content of rat renal proximal tubule suspensions was elevated two- to fivefold when incubated at 37 degrees C for 1 h with nicotinamide, 5-methylnicotinamide, or picolinamide at 1-3 mM and in the presence of a phosphodiesterase inhibitor. Thymidine had no effect on cAMP content. There was significant and specific inhibition of BBM transport of phosphate when proximal tubules were incubated with either nicotinamide or picolinamide at concentrations that increased tubule cAMP content. Thymidine had no effect on BBM transport of phosphate. These findings were independent of the dietary Pi intake of the rats. The absence of any effect of thymidine on phosphate transport strongly suggests that inhibition of poly(adenosine diphosphate ribose) polymerase does not play a role in nicotinamide action on phosphate transport. The change in phosphate transport induced by nicotinamide occurred with no change in NAD content. These findings indicate that an increase in cAMP, rather than NAD, is the important change that may mediate the acute inhibition of Na(+)-dependent phosphate transport by nicotinamide.

Sheep digoxin antibody was incorporated in liposomes, such that its biological activity was retained. Antibody incorporation was dependent on lipid composition of liposomes and was consistently greatest with the phosphatidylcholine/cholesterol/phosphatidic acid (in a 10:2:1 weight ratio) composition as compared to compositions in which the charged lipid was replaced by dicetylphosphate [bis(hexadecanyl)phosphate] or stearoylamine (octadecanylamine). Digoxin antibodies, whether injected free or as antibody‐liposome complexes, bind circulating digoxin in vivo and alter the intravascular, hepatic and splenic distribution of the cardiac glycoside. Administration of free antibody results in an intavascular retention of the digoxin label, whereas liposome‐antibody complexes were able to remove digoxin to the liver and spleen. There appears to be a later small increase in the intravascular digoxin pool in rats receiving liposome‐antibody complexes, which is probably due to the breakdown of digoxin‐antibody‐liposome complexes in the liver and spleen. Excretory studies showed that the kidney is the major route of excretion of [3H]digoxin and its possible metabolites in rats. The liposomal antibody system seems to enhance digoxin elimination over a 72‐h period when compared with the administration of free antibody. If the eliminated digoxin proves to be in a non‐toxic form, such liposome‐antibody preparations may be of use in removing digoxin from the tissues and blood in cases of digoxin overdose. This principal may have value in the treatment of overdose with clinically toxic compounds such as cytotoxic drugs, paraquat and compounds active on the central nervous system.