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R J Bicknell

Publications and source records attributed to R J Bicknell.

At least 73 records · Page 4Linked to original sources
PubMed1987

Stress-induced disruption of parturition in the rat may be mediated by endogenous opioids.

Plasma samples were obtained before and during parturition from conscious rats implanted chronically with a jugular cannula. Rats were either allowed to remain in their nesting cage throughout parturition, or were moved immediately following the birth of the second or third pup into an empty glass chamber. The time-course of parturition was prolonged for mother rats which were moved in mid-parturition to this unfamiliar environment. However, in rats given an i.v. injection of the opioid antagonist naloxone at the time of transfer, parturition followed a normal time-course, and plasma oxytocin levels were significantly higher than in animals injected with saline. Thus our hypothesis is that stress activates opioid pathways which delay parturition by inhibiting oxytocin release. Opioid-mediated mechanisms may similarly be responsible for some problems in human parturition.

Animals↗
PubMed1986

Intracellular recordings from bovine anterior pituitary cells: modulation of spontaneous activity by regulators of prolactin secretion.

The electrophysiological properties of cultured bovine anterior pituitary cells were examined using intracellular recordings. Although all cells had high input resistances (mean 332 M omega), membrane potentials (Vm) showed a wide distribution (-32 to -80 mV). In 9 cells with low Vm (mean -38 mV) spontaneous Ca2+-dependent action potentials were observed (mean frequency 3.4 hertz). In the majority of silent cells (mean Vm -58 mV), application of TRH caused a reduction in membrane resistance and a transient hyperpolarization of Vm. This initial response was followed by a small, sustained depolarization. In 4/18 cells this depolarization led to the appearance of action potentials in previously silent cells. In 15/18 cells application of dopamine caused an increase in the membrane conductance and led to a sustained hyperpolarization of 30-35 mV. The response reversibly blocked the propagation of action potentials in spontaneously active cells. This effect could also be reversed by the dopamine receptor antagonists, sulpiride and haloperidol. In all cells, elevating the extracellular potassium concentration caused a concentration-dependent depolarization and decrease in the membrane input resistance. In some cells this effect was associated with an increased frequency of action potentials. Electrophysiological responses to TRH, dopamine, and elevated potassium were correlated with changes in the release of PRL. It is concluded that by their effects on Vm these factors modulate spontaneous electrical properties and may regulate the entry of calcium necessary for hormone secretion from lactotrophs.

Action Potentials↗
PubMed1986

Synergistic interaction in bovine pituitary cultures between growth hormone-releasing factor and other hypophysiotrophic factors.

Synthetic human pancreatic GH-releasing factor (1-44)NH2 (GRF) and acetylcholine (ACh) were shown to evoke a dose-related release of GH from cultured bovine pituitary cells with half-maximal effective doses of 0.3 and 500 nmol/l respectively. Concentrations of ACh (10 mumol/l) and GRF (25 nmol/l) which were shown to give near maximal responses when presented alone, produced highly synergistic responses when tested in combination. This synergism was related to the ACh concentration employed, and both the ACh-induced release and ACh-induced synergism were abolished by the muscarinic antagonist, atropine. A synergistic interaction was also demonstrated between GRF and concentrations of thyrotrophin-releasing hormone (TRH) and bombesin which, in the absence of GRF, failed to elicit significant GH release. Acetylcholine stimulated a similar dose-dependent release of prolactin, but GRF was ineffectual in either directly stimulating prolactin release or affecting the response to ACh or TRH. No synergistic interaction could be detected between combinations of ACh and TRH or between ACh and bombesin. The data suggest that, in the somatotroph, GRF acts through a different second messenger pathway to ACh, TRH and bombesin and that these two pathways can be activated to produce a potentiated response. Growth hormone-releasing factor is, therefore, not only a specific GH secretagogue, but may act in concert with other hypophysiotrophic factors to regulate GH secretion from the bovine anterior pituitary.

Acetylcholine↗
PubMed1986

Vasopressin, but not oxytocin, is released in response to water deprivation in conscious goats.

Plasma samples obtained at 4-h intervals from goats for at least 24 h before and then during 24 h of deprivation of water were analysed by radioimmunoassay for vasopressin and oxytocin concentrations. The samples were also analysed for osmolality and sodium concentration. The differential effect of night/day versus day/night deprivation was also studied. During the two periods before the two deprivations osmolality varied in a regular manner, with low values occurring at 08.00 h. Sodium concentration followed osmolality, whereas vasopressin did not vary during the period before deprivation. During deprivation vasopressin increased along with osmolality and sodium concentration, with the beginning of the increase occurring after the morning feed. Oxytocin levels did not increase during the period of deprivation. These results do not support the hypothesis of general release of neurohypophysial hormones in response to osmotic stimuli but instead indicate there are species variations with respect to hormonal response to water deprivation.

Animals↗
PubMed1985

Neurohypophysial opioids and oxytocin secretion: source of inhibitory opioids.

When electrical stimuli are applied to the neural stalk of the pituitary, oxytocin, vasopressin, and probably several opioid peptides also contained in nerve terminals in the gland are released: one action of the released opioids appears to be to inhibit oxytocin release by an action that has been likened to pre-synaptic inhibition. Thus, when Clarke et al. (1979) stimulated the neural stalk following intravenous injection of the opioid antagonist naloxone, they observed that the evoked oxytocin release was potentiated. In the present study we confirm this result and show that oxytocin release evoked by stimulation of the supraoptic nucleus is similarly potentiated by naloxone. This finding is consistent with the hypothesis that the opioid responsible for inhibition of oxytocin release coexists with either oxytocin or vasopressin. We further report that the specific delta-receptor antagonist ICI 174864 does not potentiate oxytocin release either in vivo or in vitro. Thus, it seems unlikely that the enkephalins, putative delta-receptor agonists present in neurohypophysial fibres, are the opioids responsible for the observed inhibition of oxytocin release.

Animals↗
PubMed1985

Effects of opioid agonists and antagonists on oxytocin and vasopressin release in vitro.

The rat neurohypophysis contains both opioid receptors and substantial amounts of endogenous opioid peptides. Inhibitory influences of opioids on the secretion of both oxytocin and vasopressin have been described. We have examined the effects of a range of opioid agonists and antagonists with differing relative selectivities towards opioid receptor subclasses on the secretion of oxytocin and vasopressin from the isolated neurohypophysis. Oxytocin and vasopressin release evoked by brief periods of electrical stimulation in control experiments was compared to evoked release in the presence of test compounds. Oxytocin release was depressed approximately 25% by the delta-agonist (D-Ala2, D-Leu5)-enkephalin but not affected by putative kappa-agonists or by beta-endorphin. The use of opioid antagonists revealed a strong inhibition of oxytocin secretion by endogenous opioids released during electrical stimulation. Naloxone, relatively mu-selective, enhanced oxytocin secretion by up to 90% with a half-maximal effect at approximately 10(-6) M. MR2266, a relatively kappa-selective antagonist also enhanced oxytocin secretion but displayed agonist-like activity at high concentrations. ICI 154129, a delta-selective antagonist, was without effect on oxytocin secretion. Vasopressin release was unaffected by any of the agonists tested and not potentiated by antagonists at a range of stimulation frequencies. The data do not support the suggestion of an inhibitory endogenous opioid influence over vasopressin secretion within the neurohypophysis but indicate that an endogenous opioid peptide, possibly acting via mu- or kappa rather than delta-receptors, strongly suppresses the secretion of oxytocin.

Animals↗
PubMed1985

Central opioids: a possible role in parturition?

Pregnant rats were implanted with subcutaneous minipumps to deliver either naloxone or saline. The time-course of subsequent parturition was different between the two groups: the interval between successive births was significantly shorter for the naloxone-treated rats. This supports the hypothesis that the opioid innervation of the neurohypophysis, which is known to influence oxytocin release profoundly, has a physiological role in parturition. To test the further hypothesis that this role is particularly important in a stressful environment, pregnant rats, again implanted with minipumps, were regularly transferred, at 15-min intervals beginning with the birth of the first pup, between their normal cage and the unfamiliar environment of a glass observation chamber. No difference was noted between the time-courses of parturition for the naloxone- and saline-treated groups, although the time-courses were markedly altered from those observed in rats not subjected to an unfamiliar environment. We conclude that opioid modulation of oxytocin release may play a role in 'spacing' the delivery of successive births during normal parturition.

Animals↗
PubMed1985

Endogenous opioid peptides and hypothalamic neuroendocrine neurones.

This consideration of the influence of endogenous opioid peptide systems on GnRH and oxytocin neurones serves to illustrate some of their possible regulatory interactions with other neuroendocrine systems. Opioids are known to influence the secretion of all the anterior pituitary hormones (see Grossman & Rees, 1983) and these effects are likely to be mediated, at least in part, in the hypothalamus. For example, inhibitory effects of opioids have also been described on secretion from the median eminence of somatostatin (Drouva et al. 1981b) and dopamine (Wilkes & Yen, 1980), and this site of action probably accounts for at least some of the stimulatory effects of exogenous opioids on plasma growth hormone and prolactin levels respectively. For the GnRH neurones the influence of endogenous opioid neurones, possibly the arcuate beta-endorphin system, appears to be mediated indirectly by inhibiting release of excitatory or facilitatory monoamines. This opioid-adrenergic interaction itself appears to be central in the regulation of gonadotrophin secretion and mediation of the feedback effects of gonadal steroids in the brain. The steroids may act directly on both adrenergic and opioid neurones, altering monoamine metabolism and release which may, in turn, regulate numbers of adrenergic receptors perhaps located on the GnRH neurones. Opioid peptide levels are also modulated by steroids probably reflecting altered synthesis and/or processing of precursors. Regulation of the opioid-adrenergic input may not only acutely affect the secretory output of the GnRH neurones but also influence synthesis or processing of GnRH itself (see Kalra & Kalra, 1984) and its degradation by hypothalamic peptidases (Advis, Krause & McKelvy, 1983). Oxytocin neurones demonstrate three further levels of interaction with endogenous opioid peptides. First the anatomical organization of the oxytocin neurones has enabled a clear demonstration of the action of opioids close to the secretory terminals to uncouple the generation of electrical activity from release of peptide. Secondly, both the oxytocin and the neighbouring vasopressin neurones themselves synthesize, process and package opioid peptides. These neurones thus provide a clear example of co-existence of several biologically active products in individual neurones. The relative expression of the different gene products may prove to be a further level of control of opioid influences on the oxytocin and vasopressin neurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Different sodium requirements for 86Rb efflux and for growth hormone and prolactin secretion from bovine anterior pituitary cells.

The sodium dependence of growth hormone and prolactin secretion and of 86Rb efflux from bovine anterior pituitary cells in response to acetylcholine and TRH was examined. Decreasing the external sodium concentration prevented the increases in the rates of 86Rb efflux and of growth hormone secretion caused by acetylcholine, or by TRH in the presence of IBMX. The growth hormone secretory response was less sensitive to sodium removal than was 86Rb efflux. However, even complete removal of extracellular sodium did not affect TRH-induced prolactin secretion. Ouabain and low extracellular potassium, which inhibit the sodium pump and increase intracellular sodium, prolonged the secretion of growth hormone in response to acetylcholine, but TRH-induced prolactin secretion was not affected. Inhibition of the sodium pump speeded the decline in the 86Rb efflux rate following stimulation by both acetylcholine and TRH. The results suggest that a sodium-dependent step is necessary for the efflux of 86Rb and for growth hormone secretion but not for prolactin secretion. The possible relationship between 86Rb efflux and hormone secretion from lactotrophs and somatotrophs is discussed.

Acetylcholine↗
PubMed1984

Reversible fatigue of stimulus-secretion coupling in the rat neurohypophysis.

Single rat neurointermediate lobes were impaled on a stimulating electrode and continuously perifused with oxygenated medium. The secretion of oxytocin and vasopressin into the medium was measured by specific radio-immunoassays. The temporal profile of vasopressin release during a 20 min period of 13 Hz stimulation was compared with that of oxytocin. The results indicate that although the rate of secretion of both oxytocin and vasopressin declines over 20 min, the extent and time course of this fatigue is different for the two hormones. This difference could not be accounted for by differences in the rate of diffusion of released hormone from the tissue which was similar to the rate of wash-out of [14C]sucrose from the extracellular space in pre-labelled glands. In separate experiments glands were exposed to a prolonged period (60-70 min) of 13 Hz stimulation interrupted by brief silent periods (30 s-2 min duration). Some recovery from the fatigue of vasopressin secretion was evident after even the shortest of these silent periods. In further experiments glands were stimulated electrically for 18, 36, 54 and 72 s at 13 Hz: the order of presentation of the periods of stimulation was randomized between experiments. The vasopressin release rate declined markedly and progressively between 18 and 72 s. In contrast, the oxytocin release rate was relatively uniform throughout 72 s of stimulation. Thus vasopressin secretion is subject to a relatively rapid and dramatic fatigue. The results support the hypothesis that the phasic discharge patterns characteristic of vasopressin secreting neurones optimize the efficiency of vasopressin release from the nerve terminals in the neurohypophysis by avoiding the fatigue of stimulus-secretion coupling that accompanies continual stimulation.

Animals↗
PubMed1984

Facilitation of vasopressin release from the neurohypophysis by application of electrical stimuli in bursts. Relevant stimulation parameters.

The physiological significance of the 'bursting' pattern of firing exhibited by activated vasopressin-secreting neurones was investigated by delivering bursts of electrical stimuli to isolated rat neurohypophyses incubated in vitro and by determining vasopressin release. The stimuli were delivered in bursts at three different average frequencies (2.5, 5.0, and 7.5 Hz). For each average frequency, stimuli were delivered at a constant 10 Hz, and the durations of the burst and silence periods were altered, so that the stimulator was switched on for 25, 50 or 75% of the total time. The burst duration varied from 2.5 to 30 s. The vasopressin release generally increased with the average frequency of stimulation, but varied widely for different burst durations. The vasopressin release per stimulus pulse was found to correlate extremely well (r2 = 0.91) with burst durations of up to 20 s, regardless of the average frequency. If it is assumed that complete recovery from the effects of each burst of stimuli took place during the intervening silence periods, it can be shown that vasopressin release per burst increased as the square of burst duration. By analogy with other neurosecretory systems, facilitation of calcium entry during the bursts may be responsible.

Animals↗
PubMed1983

Oxytocin release is inhibited by opiates from the neural lobe, not those from the intermediate lobe.

Previous experiments have shown that the amount of oxytocin released by electrical stimulation from an isolated rat neurointermediate lobe is about doubled in the presence of the opiate antagonist naloxone. To test whether the opiates from the intermediate lobe inhibit the release of oxytocin, we performed similar experiments on the isolated neural lobe, after almost total removal of intermediate lobe tissue. The potentiating effect of naloxone upon oxytocin release was undiminished, suggesting that the endogenous opiate responsible for inhibiting oxytocin secretion comes from the neural lobe itself.

Animals↗
PubMed1983

Bombesin stimulates growth hormone secretion from cultured bovine pituitary cells.

Bombesin-like peptides are present in the mammalian hypothalamus. It has previously been reported that synthetic bombesin elevates plasma growth hormone (GH) and prolactin (PRL) concentrations in rats. To investigate whether bombesin has a direct action on the pituitary gland we measured GH and PRL secretion from 5-day cultures of bovine anterior pituitary cells. We compared the effects of bombesin with those of a previously described synthetic pentapeptide which releases rat GH in vitro (GHRP) and with the effects of acetylcholine which stimulates bovine GH secretion. Bombesin stimulated GH but not PRL secretion from pituitary cultures during 90-min incubations. Maximal stimulation to 157 +/- 16% of the control value was seen with 1.2 X 10(-7) M bombesin. Half-maximal stimulation occurred with 5 X 10(-9) M bombesin. The pentapeptide GHRP also stimulated GH but not PRL secretion. Maximal stimulation to 207 +/- 14% of the control value was seen with 1.3 X 10(-5) M GHRP. Half-maximal stimulation occurred with 10(-7) M GHRP. Acetylcholine stimulated secretion of both GH and PRL, both responses being abolished by the muscarinic antagonist atropine. Maximal stimulation with 10(-4) M acetylcholine was to 381 +/- 33% of the control value for GH and to 134 +/- 5% of the control value for PRL. The effects of bombesin and GHRP on GH secretion were not additive whilst the effects of both peptides were additive with those of acetylcholine. The data suggest that the synthetic GHRP peptide may possibly interact with native bombesin receptors on pituitary somatotrophs and that bombesin or a related peptide may act in vivo as a GH releasing factor.

Acetylcholine↗
PubMed1982

Inhibition by dopamine of 86Rb efflux and hormone secretion from bovine anterior pituitary cells perifused in the presence of acetylcholine or TRH.

The effects of dopamine (10(-5) M) on growth hormone and prolactin secretion and the fractional rate of 86Rb efflux were investigated using perifused bovine pituitary cells. Dopamine decreased the control efflux rate, prevented the rise caused by thyroliberin (10(-7) M) in the presence of 3-isobutyl-1-methylxanthine (10(-4) M) and greatly decreased the rise caused by acetylcholine (2.5 x 10(-5) M). Under these conditions it inhibited the prolactin secretion but it had no effect on growth hormone secretion induced by either treatment. Dopamine receptors in lactotrophs are therefore coupled to secretion and potassium permeability, but if somatotrophs contain dopamine receptors they are coupled only to K+ efflux.

1-Methyl-3-isobutylxanthine↗