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Biomedical subjects

I C Robinson

Publications and source records attributed to I C Robinson.

At least 127 records · Page 7Linked to original sources
PubMed1982

Effects of anti-oxytocin serum in Brattleboro rats.

Brattleboro rats were housed singly in metabolic cages and continuously infused with saline. Timed urine collections were analyzed for Na+ and K+; oxytocin (OT)-like material was estimated by RIA. OT infusions reduced urine flow and increased Na+ output. Urinary Na+/K+ ratios rose during OT infusion, falling below control values after infusion. Passive immunization with an OT antiserum reduced but did not prevent these renal effects of OT. In a second experiment, immunization had no effect on daily urine volume or Na+ output, even though high titers were achieved and excretion of endogenous OT-like material was reduced. We conclude that endogenous OT has little effect on Na+ excretion in these rats, although pharmacological doses of OT produced their known natriuretic effect.

Animals↗
PubMed1982

Oxytocin and neurophysin in plasma and CSF during suckling in the guinea-pig.

Cerebrospinal fluid (CSF) obtained from the cisterna magna of conscious unrestrained guinea-pigs was assayed for oxytocin (OT), vasopressin (AVP) and neurophysin (NP). Basal levels of OT and AVP were approximately 5 and 15 fmol/ml, respectively, whereas NP levels were considerably higher (around 1 pmol/ml); there was no significant differences between males, females and lactating females. In lactating females, simultaneous samples of blood and CSF were obtained during suckling episodes. Despite large increases in plasma OT and NP at milk ejection, CSF levels remained unchanged throughout. Intracerebroventricular injection of 100 fmol OT produced an 8-fold rise in the concentration of this peptide in cisternal fluid within 10 min. Since CSF levels of OT and NP do not change when these peptides are released from the pituitary, we conclude that the presence of these peptides in CSF reflects activity of extrapituitary terminals and that these terminals are not activated during suckling.

Animals↗
PubMed1982

Differential clearance of neurophysin and neurohypophysial peptides from the cerebrospinal fluid in conscious guinea pigs.

The clearance of neurohypophysial peptides from cerebrospinal fluid (CSF) in conscious unrestrained guinea pigs. 125I-labelled peptides were detectable in the cisterna magna within 2 min of their intracerebroventricular injection, reaching peak concentrations 10-15 min post-injection and declining exponentially over the next hour. 125I-oxytocin (125I-OT) and 125I-vasopressin (125(I-AVP) were cleared at similar rates, whereas 125I-labelled neurophysin (125I-NP) disappeared significantly more slowly; mean half-times of clearance (t1/2) from cisternal CSF were 28, 24 and 46 min, respectively. 125I-NP was cleared at the same rate as 3H-inulin (t1/2 40 min), as was an antibody to OT (anti-OT, t1/2 37 min). Intracerebroventricular infusions of iodinated peptides produced constant levels in CSF within 3 h. 125I-AVP reached lower plateau levels and disappeared twice as fast as 125I-NP, although the apparent equilibrium distribution space was the same for both peptides. Although NP was cleared half as fast as OT or AVP, this difference was not sufficient to account for the large molar excess of NP over the nonapeptides in guinea pig CSF. There is an effective blood/CSF barrier to neurohypophysial peptides in the guinea pig; intravenous infusions of OT or porcine NP did not raise the CSF levels of these peptides (measured by specific radioimmunoassays) except when very high concentrations were maintained in peripheral plasma. However, single intravenous injections of anti-OT produced low but significant titres in CSF, persisting for several days.

Animals↗
PubMed1982

Activation and clearance of a hormonogen, triglycyl-oxytocin, in the conscious dog.

Triglycyl-oxytocin (TGOT) and oxytocin (OT) were administered iv and sc to conscious dogs and the plasma concentrations of these peptides determined simultaneously by RIA and bioassay. Constant iv infusions (1 h) at 23 pmol/kg/min produced plateau levels of 1.1 and 1.6 pmol/ml plasma for OT and TGOT respectively. Whilst the distribution space was similar for each peptide. TGOT persisted longer in the circulation (t1/2, for TGOT 6.6 min; for OT 4.2 min). Bioactive values for OT followed RIA values whether this peptide was given iv or sc. Although very little bioactivity was generated by iv infusions of TGOT, considerable amounts of bioactive OT were found in plasma after injection of TGOT subcutaneously. The hormonogen proved relatively resistant to oxytocinase, an enzyme that destroys OT rapidly. Our results indicate that TGOT is converted to OT in vivo and that its action as a hormonogen is more pronounced after sc than iv administration.

Animals↗
PubMed1982

Oxytocin, vasopressin and neurophysins in the hypothalamo-neurohypophysial system of the human fetus.

The content of vasopressin, oxytocin and their related neurophysins was measured in the hypothalamus and pituitary gland of mid-trimester human fetuses. Vasopressin was present in both tissues approximately 3-4 weeks before oxytocin. The levels of the hormones in the pituitary gland increased 1000-fold over the next 3-4 months. During this time, the very high vasopressin/oxytocin ratio gradually deceased but did not reach unity in the period studied. In contrast, both the vasopressin-associated neurophysin and the oxytocin-associated neurophysin appeared in the pituitary gland at the same gestational age and showed the same exponential increase with fetal age. Lower levels of the neurophysins and the nonapeptides were found in the hypothalamus and the levels increased more slowly with fetal age. Our results suggest that the high vasopressin/oxytocin ratios observed in fetal life are due to differences in the rate of maturation of the hormone precursor, rather than to differences in the rate of de-novo synthesis.

Female↗
PubMed1981

A method for repeated sampling of cerebrospinal fluid from conscious guinea pigs.

A new method is described for obtaining repeated cerebrospinal fluid (CSF) samples from conscious, unrestrained guinea pigs. A simple, disposable cannula is introduced into the cisterna magna by puncturing the atlanto-occipital membrane. The cannula is equipped with a silicone rubber disc which is glued to the membrane, forming a firm but flexible seal. Daily CSF samples of at least 100 microliters can be obtained from unrestrained guinea pigs. Chronically cannulated lactating females continued to suckle their litter successfully, and their milk ejection response was not affected by withdrawal of CSF.

Animals↗
PubMed1981

Suckling in the guinea-pig: the simultaneous release of oxytocin and neurophysin.

The release of oxytocin and neurophysin during suckling has been studied in conscious unrestrained guinea-pigs. After prior separation, mothers and litters were allowed to suckle for a period of 10 min, and the weight gain of the litter recorded as an index of milk transfer. Maternal blood samples were obtained without disturbance through previously implanted intravenous cannulae and neurophysin and oxytocin determined on unextracted plasma by specific and sensitive radioimmunoassays. In 82 out of 118 experiments the young gained weight during suckling (1.6 +/- 0.1 (S.E.M.) g/pup) and this was associated with large rises in both oxytocin and neurophysin concentrations in plasma (mean concentrations: oxytocin 65.4 fmol/ml, neurophysin 360 fmol/ml). Where serial samples were taken, oxytocin and neurophysin showed a rapid rise and fall in concentration closely associated with the occurrence of milk ejection as judged by the behaviour of the litter. The present results provide the first direct evidence of a spurt release of both oxytocin and neurophysin measured simultaneously during milk ejection. The conscious lactating guinea-pig thus provides a useful laboratory model in which to study hormone release during milk ejection.

Animals↗
PubMed1981

Suckling in the guinea-pig: the effects of passive immunization with an antiserum to oxytocin.

Lactating guinea-pigs were passively immunized with an antiserum to oxytocin of high titre, specificity and avidity. Single i.v. injections of 0.1-0.4 ml antiserum produced high titres which decayed slowly (half-life congruent to 7 days). Passively administered antiserum was effective in vivo; the clearance of exogenous oxytocin from plasma was greatly slowed in immunized animals. Passive immunization with 0.4 ml antiserum reduced milk transfer to the litter during suckling episodes of 10 min, and overall litter growth rates were significantly decreased. Non-immune serum was without effect. Plasma neurophysin levels showed the same large rises during suckling in immunized animals, indicating that neurohypophysial activation was unimpaired. Despite the presence of high titres of antiserum, some milk transfer still occurred at milk ejection. In-vitro experiments showed that more than 25% of oxytocin remained free 20s after mixing with plasma taken from passively immunized animals. It is probable that the antiserum in the circulation was unable to bind all the oxytocin released from the posterior pituitary gland before it reached the mammary gland.

Animals↗
PubMed1980

The development and evaluation of a sensitive and specific radioimmunoassay for oxytocin in unextracted plasma.

The development and evaluation of a radioimmunoassay for oxytocin is described. High titre antisera were raised to oxytocin coupled to thyroglobulin and tested for specificity with a number of oxytocin analogues and fragments. Two antisera showing high specificity were used to assay plasma directly without extraction. The maximum sensitivity was 0.5pg per tube and the intra- and inter-assay co-efficients of variation were 7.1 and 11.6% respectively. Cross-reactivity studies indicate that the antisera were directed chiefly to the oxytocin side-chain. The antisera could be purified by affinity chromatography using this tripeptide coupled to agarose beads but this did not improve their avidity or specificity. The assay was tested successfully with a number of body fluids and tissue extracts, although human late-pregnancy plasma could not be added directly to the assay. Direct radioimmunoassay was used to estimate the clearance of oxytocin infused into conscious dogs, and good agreement was found when the same samples were also bioassayed. The antisera also efficiently neutralise the biological activity of oxytocin in vivo and in vitro.

Animals↗
PubMed1979

Extraction of small amounts of oxytocin from biological fluids by means of agarose-bound neurophysin.

The use of agarose-bound neurophysin for the extraction of oxytocin from biological fluids is described. Oxytocin can be extracted from plasma, urine and cerebrospinal fluid with a high rate of recovery and samples varying widely in volume and oxytocin concentration can be tested by the method. Columns can be used to extract and concentrate dilute samples, or to help identify small amounts of neurohypophysial hormones by affinity chromatography. The oxytocin can be eluted from the column directly into the buffer used for subsequent bioassay. The composition of the final extract is constant and independent of the composition of the sample. The specificity of the binding is high. It is suggested that the method has many advantages over others in current use.

Animals↗
PubMed1976

Calcium and stimulus secretion coupling in the neurohypophysis. V. The effects of the Ca2+ ionophores A23187 and X537 A on vasopressin release and 45Ca2+ efflux; interactions with sodium and a verapamil analogue (D600).

Slices from ox neurohypophyses were incubated in a calcium-free medium with the ionophores A23187 or X537A. X537A (5 X 10(-5) mol/l) caused a marked release of vasopressin, neurophysin and protein to the medium. A23187 (2 X 10(-5) mol/l) did not cause any release by itself, but when Ca2+ was added to the medium in the presence of the ionophore, an increase in the release of vasopressin, neuorphysin and protein occurred. Release of lactate dehydrogenase and peptidase were not affected by the ionophores. The secretion caused by A23187 was abolished by D600 (a verapamil analogue) (2 X 10(-5) mol/l) whereas the effect of X537A was unchanged. The effects of X537A were strongly inhibited by removal of sodium from the medium. Re-addition of sodium to the medium caused a marked release. Gramicidin (10(-6) or 5 X 10(-5) mol/l) had no effect on secretion. Efflux of 45Ca2+ from pre-loaded slices was drastically reduced in a sodium-free medium. X537A caused an increase in the efflux rate of 45Ca2+ both in medium with a normal concentration of sodium and when slices had been incubated in a sodium-free medium. A23187 and X537A both released 45Ca2+ from a neurohypophyseal mitochondrial fraction. When sodium in a concentration of 20 mmol/l was added to this fraction, the Ca2+ accumulation was inhibited. This effect was reduced by inorganic phosphate up to a concentration of 2 mmol/l.

Animals↗
PubMed1974

Bioassay of oxytocin on the superfused mammary gland of the mouse, using an automatic apparatus.

1 A sensitive method of assaying oxytocin using the superfused mouse mammary gland is described. The method is shown to be reliable, accurate and precise. Assays are performed automatically and the preparation is stable for at least 18 hours.2 The preparation is relatively insensitive to bradykinin, histamine, 5-hydroxytryptamine, angiotensin, prostaglandin F(2alpha), adrenaline and noradrenaline. The contractions produced by acetylcholine can be abolished by atropine without the sensitivity to oxytocin being affected.3 Vasopressin has a variable activity on the preparation; its potency can be as high as one-fifth that of oxytocin.4 It is concluded that this method compares favourably with other published methods.

Acetylcholine↗