Search PubMed⌕ Search

Biomedical subjects

R J Bicknell

Publications and source records attributed to R J Bicknell.

86 records · Page 5Linked to original sources
PubMed1981

Role of cyclic nucleotides in the inhibition of growth-hormone secretion by somatostatin.

The effects of somatostatin on GH secretion, cyclic AMP and cyclic GMp concentrations in dispersed bovine anterior pituitary cells were studied following activation of adenylate cyclase with cholera toxin and inhibition of phosphodiesterase with isobutylmethylxanthine (IBMX). Cholera toxin (10(-5)M) increased intracellular cyclic AMP concentration 10-fold and cyclic GMP concentration 3-fold relative to control, and stimulated the secretion of GH. IBMX (10(-4) M) als increased intracellular concentrations of both cyclic AMP and cyclic GMP and the secretion of GH and potentiated the actions of cholera toxin particularly in raising intracellular cyclic AMP concentrations which were elevated 40-fold in the presence of cholera toxin and IBMX. Somatostatin (5 X 10(-7) M) completely prevented GH secretion elicited by cholera toxin and/or IBMX. Somatostatin was without effect on control cyclic AMP and cyclic GMp concentrations and on the increases in both cyclic AMP and cyclic GMP caused by cholera toxin and by IBMX alone, or in combination. The data suggest that bovine GH secretion is increased when concentrations of either or both cyclic nucleotides are elevated within the cells, although incubation of cells with extracellular concentrations of cyclic AMP and cyclic GMP derivatives up to 2 x 10(-3) M caused only small changes in GH release. We suggest that somatostatin inhibits cholera toxin-induced bovine GH secretion by preventing activation of the secretory process by either cyclic AMP or cyclic GMP.

1-Methyl-3-isobutylxanthine↗
PubMed1981

Inhibition by somatostatin of bovine growth hormone secretion following sodium channel activation.

1. Growth hormone secretion, exchangeable cellular sodium and calcium concentrations measured by 22Na and 45Ca incorporation, and efflux of 45Ca were studied in dispersed bovine anterior pituitary cells. 2. Addition of veratridine (100 microM), an activator of sodium channels, increased exchangeable sodium and calcium concentrations in the cells, the efflux of 45Ca from prelabelled cells, and caused a biphasic stimulation of the rate of growth hormone secretion. Secretion of growth hormone was not stimulated when the extracellular calcium was decreased below 0.1 mM. 3. The increases in growth hormone secretion, exchangeable calcium concentration and 45Ca efflux from prelabelled cells caused by veratridine were abolished by addition of the calcium antagonist verapamil (20 microM). Verapamil also reduced the rise in exchangeable sodium caused by veratridine and increased the resting exchangeable sodium concentrations. 4. The peptide somatostatin (1 micrograms/ml) prevented veratridine-stimulated growth hormone secretion but did not inhibit the increases in exchangeable sodium and calcium caused by veratridine. The peptide itself elicited a transient increase in 45Ca efflux and subsequently partially inhibited veratridine-stimulated 45Ca efflux. 5. The data suggest that anterior pituitary cells possess voltage-sensitive sodium channels. Activation of these channels by veratridine may lead to depolarization and increased entry of calcium via potential-dependent calcium channels, which contributes to a rise in cytoplasmic calcium concentration and the subsequent stimulation of growth hormone secretion. We conclude that the calcium antagonist verapamil may also interact with sodium channels, and that the peptide somatostatin may act on growth-hormone-secreting cells either to prevent the rise in cytoplasmic calcium by hyperpolarizing the cells or to decrease the affinity of a population of calcium binding sites in the cells.

Animals↗
PubMed1981

Relative efficiency of neural firing patterns for vasopressin release in vitro.

Single rat neurohypophyses were impaled on a platinum electrode, perifused with isotonic medium and fractions of perifusate collected each minute. Arginine vasopressin content of the fractions was measured by radioimmunoassay. The basal release of arginine vasopressin varied from 50 to 350 pg (0.02-0.14 mU/min) between individual neurohypophyses. Recordings previously obtained from rat supraoptic neurones provided the patterns for electrical stimulation. 8-min segments of a phasically and a continuously firing neurone were selected such that each was firing at a mean rate of 6 spikes/s and possessed very similar overall distributions of interspike intervals. In 15 experiments individual neurohypophyses were stimulated with the phasic pattern, followed by the continuous pattern, or vice versa, separated by an 8-min unstimulated period. In either case, significantly more hormone was released during phasic stimulation than during continuous stimulation. It is concluded that the phasic firing pattern typical of vasopressin neurones is highly efficient for the release of vasopressin from the neurohypophysis, but that its effectiveness does not lie in an increased preponderance of short interspike intervals.

Animals↗
PubMed1979

Acetylcholine stimulates growth hormone secretion, phosphatidyl inositol labelling, 45Ca2+ efflux and cyclic GMP accumulation in bovine anterior pituitary glands.

Acetylcholine (25 micromol/l) in the presence of the choline esterase inhibitor physostigmine (67 micromol/l) increased the release of growth hormone and efflux of 45Ca2+ from perifused bovine pituitary slices; the time taken for the maximal response to occur was the same. In batch incubations, acetylcholine (1 micromol/l--1 mmol/l) increased pituitary cyclic GMP concentrations in the pituitary gland within 2 min, and increased incorporation of [3H]inositol and [32P]phosphate into pituitary phosphatidyl inositol within 15 min. Cyclic AMP concentrations were not significantly changed 2 or 5 min after acetylcholine addition. All the tissue responses were inhibited by prior exposure of the tissue to atropine (1 micromol/l) but not by tubocurarine (10 micromol/l--1mmol/l), indicating that the responses were mediated by receptors of the muscarinic type. The similarities between these responses and those to known hypothalamic hypophysiotrophic hormones are discussed.

Acetylcholine↗
PubMed1978

Effects of somatostatin and verapamil on growth hormone release and 45Ca fluxes.

Increasing the extracellular K+ concentration to 71 mM causes a phasic release of growth hormone and efflux of 45Ca from perifused bovine pituitary cells. Verapamil (20 micron) partially inhibits the initial phase of growth hormone release and 45Ca efflux and completely inhibits the second phase. Somatostatin (1 microgram/ml) partially inhibits both phases of growth hormone release but does not modify 5+-induced 45Ca efflux. Incubation of pituitary cells in 71 mM K+ increases 45Ca incorporation; verapamil (20 micron) completely prevents, and somatostatin (1 microgram/ml) partially inhibits, the K+-induced increase in 45Ca incorporation. The results suggest that 71 mM K+ increases both calcium entry into the cells and calcium redistribution within them, and that verapamil only inhibits the K+-induced calcium entry. Somatostatin may inhibit calcium entry into tissue stores.

Animals↗
PubMed1976

The half-life of luteinizing hormone in intact and castrated quail during photoperiodic stimulation.

In the Japanese quail (Coturnix coturnix japonica) the plasma concentration of luteinizing hormone (LH) depends on the physiological state of the animal. Low levels are found in sexually immature birds on short days (0.8 +/- 0.1 (n = 20) ng/ml) while after exposure to long days, sexually mature birds have a significantly higher LH level (4.4 +/- 0.4 (n = 20) ng/ml). Castration of long day males results in an even higher rise in LH concentration to 16.8 +/- 1.8 (n = 16) ng/ml. When the half-life (t1/2) of circulating LH was determined it was found to have two components: a fast t 1/2 of about 6 min and a slower component of either 20 min (determined by a radioisotope method), or 40 min (following hypophysectomy). No significant difference was observed in either of these components between birds in the three physiological states (short days, long days, castration plus long days). It would appear, therefore, that since the half-life of plasma LH remains constant, the difference in circulating LH observed under the various physiological conditions results solely from a change in the rate of LH secretion.

Animals↗