Effects of taste stimulation on beta-endorphin levels in rat cerebrospinal fluid and plasma

Opioids are suggested to be involved in generation of palatability and facilitation of consumption of food and fluid. We measured the level of an endogenous opioid, beta-endorphin, in the cerebrospinal fluid (CSF) and plasma after free drinking of water and taste solutions in Wistar rats. When the water-deprived animals were allowed to drink 10 mL of water, the level of beta-endorphin increased significantly 60 and 90 min after the start of drinking in both samples. beta-Endorphin in the CSF increased most after ingestion of 0.5 M sucrose and 0.005 M saccharin followed by 0.1 M NaCl, 0.1 mM quinine and water. An intragastric infusion of 7 mL of water did not change the beta-endorphin level. Essentially the same results were obtained for plasma samples except that NaCl and quinine solutions did not increase beta-endorphin levels. Sucrose became ineffective in releasing beta-endorphin in both samples after the establishment of conditioned taste aversions to this taste stimulus. These results suggest that the release of beta-endorphin is positively correlated with the palatability of taste stimuli, and that CSF beta-endorphin also reflects the reinforcement of fluid intake in thirsty animals.     

Instrumentation for cerebrospinal fluid hydrodynamic studies in man

Instrumentation developed for the direct study of the human cerebrospinal fluid (c.s.f.) system is described. The configuration consists of a servo pressure regulator, two pressure transducers, a special function generator, an electronic pressure limiter, a strain-gauge balance, a volume and flow-rate meter, a c.s.f. conductance calculator, a 4-channel pen recorder, an x/y pen recorder and an ink-jet recorder. It is possible to regulate the c.s.f. pressure to any value between — 2·0 and 10.0 kPa or to regulate the flow rat of fluid into or out of the patient or to perform simple bolus injections/withdrawals. The c.s.f. model used allows indirect calculation of the pressure in the sagittal sinus and the pressure difference between the subarachnoid space and the sagittal sinus. The instrumentation is currently used for the study of c.s.f. pressure, c.s.f. formation rate, c.s.f. absorption rate, conductance of c.s.f outflow pathways, c.s.f. pressure/volume relationship and neurosurgical shunt systems. We have shown that the method of constant-pressure c.s.f infusion is faster than the method of constant-flow-rate c.s.f. infusion in obtaining reliable measuremnts of c.s.f. outflow conductance.     

Substance P and nasal secretion in dog, rat, and man

The effect of substance P (SP) on nasal secretion was studied in dog, rat, and man. Substance P was administered topically by the use of filter papers that had been soaked with an aqueous solution of SP and dried. The SP-containing filter paper strips were applied to the nasal mucosa for five minutes. The secretion was absorbed onto the filter papers. The strips were weighed before and after the experiment. Substance P induced atropine-resistant nasal secretion in a dose-dependent manner in anaesthetized dogs and rats. In man, SP failed to evoke nasal secretion in the doses applied. Systemic effects limited the dose that could be given to man. When exposed to nasal secretions SP was rapidly degraded. This may explain the failure of SP to evoke nasal secretion in man.     

Measurement of tele-methylhistamine and histamine in human cerebrospinal fluid,urine, and plasma

A gas chromatographic-mass spectrometric method described by us to measure tele-methylhistamine (t-MH) in brain was used to measure t-MH in human cerebrospinal fluid (CSF), urine and plasma. The presence of t-MH in these body fluids was rigorously established. No pros-methylhistamine could be detected, and it was used as internal standard to quantify t-MH in the fluids. The mean levels of t-MH were: urine, 943 pmol/mg creatinine; plasma, 12.3 pmol/ml; and CSF, 2.2 pmol/ml. Parallel measurements of histamine by a radioenzymatic method showed, respectively, 182 pmol/mg creatinine; 19.5 pmol/ml; and 388 pmol/ml. The levels of HA in CSF, much higher than those of its metabolite, t-MH, are high enough to stimulate HA receptors in the central nervous system.     

The transport of L-tryptophan from cerebrospinal fluid in the dog

1. Endogenous tryptophan is uniformly distributed in dog cerebrospinal fluid (c.s.f.) and is about one tenth of the normal fasting plasma level.2. Using a recirculatory ventriculo-cisternal perfusion technique in conscious dogs it was found that L-tryptophan was removed from c.s.f. by a non-saturable mechanism in addition to bulk absorption of c.s.f. The clearance of L-tryptophan from c.s.f. was unaffected by thiopentone anaesthesia.3. Dialysis of dog plasma against an artificial c.s.f. solution containing L-tryptophan demonstrated that a large proportion of the tryptophan in dog plasma was protein-bound and that the unbound diffusible proportion would equilibrate with tryptophan concentrations equivalent to those normally found in dog c.s.f.4. Use of an open-circuit ventriculo-cisternal perfusion system in unanaesthetized dogs revealed the presence of a saturable component in the transport of tryptophan from c.s.f.5. As [¹⁴C]L-tryptophan infused into a recirculatory perfusion system produced no radioactively labelled metabolites, it was concluded that removal of tryptophan from c.s.f. by cerebral metabolism does not contribute substantially to maintaining the low levels of tryptophan in c.s.f. but that brain uptake associated with protein-binding may give rise to a small saturable component. The results indicate that the actual concentration gradient of tryptophan between plasma and c.s.f. is much less than it appears from the total concentration of tryptophan in the two fluids, and that the mechanism by which the c.s.f. — plasma distribution of tryptophan is maintained is mainly attributable to simple diffusion.     

Immunoglobulins to tick-borne encephalitis in the cerebrospinal fluid of man

Antibodies of IgM and IgG type were detected in the CSF of patients with recent tick-borne encephalitis (TBE) by means of ELISA. No false-positive results were obtained with CSF specimens from patients suffering from meningitis or other illnesses. The ratio of the antibodies in serum to CSF clearly indicated that both IgM and IgG antibodies were produced in the brain itself. In patients who had previously suffered from TBE now with a different inaseptic meningitis, TBE antibodies could also be detected in CSF but only of the IgG class. Again the serum-to-CSF antibody ratio indicated that the antibodies were produced within the central nervous system. For routine diagnosis the micro-ELISA method was found to be useful; antigen-coated plates can be stored as long as three months at +4 degrees C.     

Regulation of angiotensinogen in cerebrospinal fluid and plasma of rats

The origin and regulation of angiotensinogen in cerebrospinal fluid (CSF) was investigated in rats by measuring renin substrate in plasma and CSF under different experimental conditions. Nephrectomy (NX) increased the circulating and the central angiotensinogen levels. There was no correlation between the individual values of plasma and CSF. Adrenalectomy (ADX) diminished and hydrocortisone treatment augmented the angiotensinogen levels in plasma and CSF. The combination of ADX and NX caused a dissociation between peripheral and central angiotensinogen, since the values were elevated in plasma but unchanged in CSF. After the application of the converting-enzyme inhibitor captopril a significant decrease of angiotensinogen was observed in plasma only. A specific radioimmunoassay for renin substrate of rat plasma also recognized CSF angiotensinogen. There was a linear correlation between the CSF substrate levels obtained by direct and indirect measurement. In conclusion, CSF angiotensinogen appears to be immunologically similar to the plasma molecule. The angiotensinogen levels in CSF and plasma may be affected in parallel but can nevertheless be dissociated from each other.     

Vasopressin levels in the cerebrospinal fluid of rats with lesions of the paraventricular and suprachiasmatic nuclei

The circadian rhythm and dehydration-induced response of vasopressin (AVP) levels in rat cerebrospinal fluid (CSF) were studied after lesions had been made in the paraventricular (PVN) and suprachiasmatic (SCN) nuclei. The rhythmic fluctuation of AVP levels in CSF was abolished after SCN lesions, whereas lesions of the PVN had no effect. Dehydration seems to increase AVP levels in CSF of both sham-operated and lesioned animals. These data further suggest that the circadian rhythm of AVP in CSF is preferentially generated by SCN. In contrast, several areas of the brain may contribute to the overall AVP levels in CSF, both under normal physiological conditions and under osmotic stress.     

Insulin responses and glucose levels in plasma and cerebrospinal fluid during fasting and refeeding in the rat

The present experiments were designed to investigate the rate of penetration of insulin from the plasma into the cerebrospinal fluid (CSF) during 24 hr of fasting and refeeding in the light phase. The results show that under these conditions basal CSF-immunoreactive insulin (IRI) levels were positively correlated with plasma IRI levels. Basal plasma IRI fell during a fast but was similar to prefast control after one day of refeeding. Although CSF-IRI levels rose during glucose infusion, CSF-IRI was not elevated by glucose during a fast. During refeeding, CSF-IRI responses returned toward control, prefeeding values. This study suggests a decreased transport of insulin from plasma to CSF during fasting. The lower CSF-IRI levels achieved under these conditions may determine meal size by allowing larger meals after a fast.     

Electrolyte and acid-base parameters of rat cerebrospinal fluid

Summary Values for various electrolytes and acid-base parameters of rat CSF were determined in adult animals anesthetized with pentobarbital or ether. In addition, the distribution of 5,5-dimethyl-2,4-oxazolidinedione (DMO) between CSF and arterial and venous blood was measured in the same animals. It was found a) that CSF electrolyte and acid-base parameters are the same in ether-and pentobarbital-treated animals; b) that DMO distributions between CSF and blood are not determined solely by pH gradients; and c) that in rat CSF electrolyte concentrations (mEq/l) —Na=148.4; K=3.16, Cl=117.9 —and acid-base values —pH=7.38, H₂CO₃=1.30 mM/l; HCO₃=24.5 mM/l —are very similar to those measured in other species.This study was supported, in part, by Grant NB 04553 from the U.S. Public Health Service, National Institutes of Health.Receipient of U.S. Public Health Service Research Career Development Program Award 1-K3-NB 7779.Receipient of U.S. Public Health Service Research Career Program Award 5-K6-NB-18, 838.