GENERAL PHARMACOLOGY OF RECOMBINANT HUMAN BASIC FIBROBLAST GROWTH-FACTOR

General pharmacological effects of recombinant human basic fibroblast growth factor (bFGF) were investigated. 1. Central nervous system: Bas ic FGF produced almost no effect on the general symptoms and behaviors of mice. Basic FGF did not influence the spontaneous motor activity, hexobarbital-induced anesthesia, electroshock seizure threshold, penty lenetetrazole-induced seizure in mice and normal body temperature and spinal reflex in rats up to a dose of 1 mg/kg (s.c., i.v.). As regards pain sensation, it inhibited the acetic acid-induced writhing at 1 mg /kg (s.c.). No abnormal waves were observed in spontaneous EEG of the rabbit up to 1 mg/kg (i.v.) of bFGF, but at 0.1 mg/kg it had a slight effect on the ratio of EEG levels and at 1 mg/kg induced an increase i n rest period, disappearance in the period of fast wave sleep and a de crease in the period of deep sleep. 2. Somatic nervous system: Basic F GF did not influence the corneal reflex, twitch response of the skin a nd diaphragm-phrenic nerve preparations. 3. Autonomic nervous system a nd smooth muscle: Basic FGF showed little effects on the spontaneous m ovement of the isolated ileum, contraction induced by various agonists in isolated ileum, resting tension and noradrenaline(NA)-induced cont raction of the aorta, resting tension and histamine-induced contractio n of isolated trachea, spontaneous movement and 5-HT-induced contracti on of isolated strips of stomach fundus, NA-induced contraction of iso lated vas deferens of the rat up to the concentration of 10(-4) g/ml. Basic FGF augmented the tone of the isolated non-pregnant uterus at th e concentrations of 10(-5) g/ml and above and inhibited or tended to i nhibit the contractile tension of non-pregnant or pregnant uterus at 1 0(-4) g/ml, but it did not influence the spontaneous movement of the u terus, either the nonpregnant or pregnant, under in situ conditions ev en at a dose of 1 mg/kg (i.v.). Basic FGF did not influence the pupil size. 4. Respiratory and circulatory systems: Basic FGF had no effect on the isolated heart. The influence was not exerted on the heart rate for the isolated atria but slight inhibition of contractile force was observed at 10(-4) g/ml. In anesthetized dogs a decrease in blood pre ssure, a slight increase in heart rate and respiratory rate and a decr ease in femoral blood flow were observed at 0.01 and 0.1 mg/kg (i.v.) of bFGF. Similarly, a slight increase in heart rate and a slight decre ase of blood pressure were observed at 1 mg/kg (s.c.) in conscious rat s. 5. Digestive system: Administration of bFGF at 1 mg/kg did not resu lt in changes in the transport capacity within the gastrointestinal tr act (s.c., i.v.) and the secretion of the gastric juice (s.c.). 6. Uri ne output and electrolyte metabolism: Basic FGF produced a decrease in urinary Na+ excretion at 1 mg/kg (s.c.), and showed a tendency to inc rease in urinary volume at 0.01 and 0.1 mg/kg (i.v.). At 1 mg/kg (i.v. ) urinary excretion of Na+ and Cl- was decreased significantly. It had no effect on the ability of rats to excrete PSP (phenol red) up to 1 mg/kg (s.c.). 7. Blood system: Basic FGF did not influence the coagula tion time of the whole blood, prothrombin time and activated partial t hromboplastin time of rats up to 1 mg/kg (s.c., i.v.). It did not infl uence the aggregation of rabbit platelets induced by collagen and ADP up to 10(-4) g/ml. Basic FGF at concentration of 10(-4) g/ml exhibited no hemolytic action. 8. Local action: Plantar subcutaneous injection of bFGF at above 0.005 mg/site induced edema by itself on and after th e next day, and also reinforced carrageenin-induced edema from 1 day a fter injection. The results show that bFGF did not produce any acute e ffects on the somatic nervous system, autonomic nervous system, smooth muscle and blood system. In contrast, bFGF produced slight effects on the circulatory system, central nervous system and kidney function wh en injected systemically. Subcutaneous administration may produce edem a at the site of injection.