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C T Jones

Publications and source records attributed to C T Jones.

At least 55 records · Page 3Linked to original sources
PubMed1990

Adrenal responses to corticotrophin-releasing factor in conscious hypophysectomized calves.

1. Adrenal responses to intra-aortic infusions of pure synthetic ovine corticotrophin-releasing factor (CRF) have been investigated in functionally hypophysectomized calves previously fitted with an adrenal clamp. 2. CRF caused an increase in the output of cortisol from the adrenal gland, which was dose related over the range 4-8 pmol min-1 and maximal at the higher of these doses; this response was observed at a dose below that which produced any change in adrenal vascular resistance. Cortisol output was also found to be related linearly to the rate at which CRF was estimated to be presented to the gland during these infusions. 3. The infusions of CRF also provoked the release of small, but readily detectable, amounts of adrenocorticotrophin-like peptides (ACTH) from the gland. This was mainly in the form of ACTH1-39 with some pro-opiomelanocortin (POMC) also being released. 4. Comparison of the adrenal steroidogenic response to exogenous CRF with that to synthetic ACTH1-24 showed that CRF was the more potent; in each case cortisol output was related linearly to the presentation rate of the peptide. 5. It is concluded that the adrenal cortex in the calf is capable of releasing cortisol in response to exogenous CRF at low concentrations and is even more sensitive to CRF than it is to exogenous ACTH over the dose range that was employed.

Adrenal Cortex↗
PubMed1990

Pregnancy suppresses G protein coupling to phosphoinositide hydrolysis in guinea pig myometrium.

The regulatory factors controlling uterine contractile activity during pregnancy remain unclear, although pathways modulating intracellular Ca2+ and prostaglandin production play an important role. Because excitatory hormones raise myometrial Ca2+ levels and prostaglandin output through increasing phosphoinositide hydrolysis, regulation of G protein coupling to phospholipase C activation could be a key site for control. To measure the functional activity of this signaling pathway, we measured formation of [3H]inositol phosphates from prelabeled guinea pig myometrial membranes in response to G protein activation by guanosine 5'-[gamma-thio]triphosphate (GTP gamma S) and fluoride. Although these agents stimulated a three- to fivefold increase in phosphoinositide phospholipase C activity in nonpregnant myometrium, at 46-47, 53-60, and 66-69 days of pregnancy (full term 67 +/- 2 days) this response fell by 43-83%. Moreover, the half-maximal effective dose (ED50) for GTP gamma S action was increased from 8.11 +/- 0.91 nM (n = 5) in the nonpregnant state to 307.4 +/- 142.3 (n = 9) and 209.7 +/- 155.1 nM (n = 8) at 53-60 and 66-69 days, respectively. Because phospholipase C levels displayed only a limited fall (28%) whether measured by direct Ca2+ activation or by immunoblotting, this study indicates a considerable suppression of G protein functional coupling to myometrial phosphoinositide hydrolysis throughout late gestation. Such a desensitization is likely to contribute to reports of diminished contractile sensitivity during pregnancy and to reflect an essential regulatory event in the processes maintaining uterine quiescence in pregnant guinea pig.

Animals↗
PubMed1990

Effect of glucocorticoids on alpha 1-adrenergic receptor binding in rat vascular smooth muscle.

Glucocorticoids are known to have marked effects on blood pressure regulation, predominantly through altering cardiovascular sensitivity to noradrenaline. However, the molecular mechanisms underlying this action remain unclear. As part of our studies into these we have measured alpha 1-adrenergic receptor binding using the ligand [3H]prazosin in plasma membrane fractions of aortas prepared from control, adrenalectomized and dexamethasone-treated adrenalectomized rats. In controls there were 50 +/- 8 (S.E.M.; n = 6) fmol alpha 1-adrenergic receptors/mg membrane protein (Bmax) with a dissociation constant (Kd) of 0.52 +/- 0.10 nM (n = 6). Adrenalectomy 8 days before tissue preparation caused a 40% decrease in Bmax and a 60% decrease in Kd. Dexamethasone replacement after adrenalectomy returned these values close to those of controls. Noradrenaline competed for the [3H]prazosin-binding sites. Computer analysis by a non-linear curve-fitting program (LIGAND) showed that noradrenaline binding was to a heterogeneous population of high- and low-affinity receptors with Kd values of 1.87 +/- 0.73 microM and 0.48 +/- 0.12 mM (n = 5) respectively. Guanosine thiotriphosphate (GTP[S]) caused the conversion of high-affinity to low-affinity binding, consistent with the model of the high-affinity sites being coupled to a G protein. After adrenalectomy, noradrenaline binding was to a homogeneous population of low-affinity receptors; hence, the effect of GTP[S] was no longer apparent, suggesting that under these conditions the alpha 1-adrenergic receptors were unable to couple to a G protein. The two-site model of binding and GTP[S] effect was returned by dexamethasone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1990

Glucocorticoids regulate the amount of G proteins in rat aorta.

Glucocorticoids are known to influence cardiovascular sensitivity to catecholamines but the molecular mechanisms are undefined. We recently showed that glucocorticoids control the coupling of adrenergic receptors to G protein. Alterations in the amount of G protein is one mechanism by which receptor-G protein coupling may be controlled. Therefore, we set out to measure the levels of G proteins in aorta from normal, adrenalectomized and dexamethasone-treated adrenalectomized rats. G proteins were measured in plasma membrane preparations by immunoblotting and horseradish peroxidase staining. After adrenalectomy there was 53% (n = 5) decrease in the density of staining for Gi (ANOVA; P less than 0.05 compared to controls). Conversely, there was a 210% (n = 5) increase in the density of staining for Gs. The levels of Go and the beta-subunit of G proteins were not changed by adrenalectomy. Dexamethasone-replacement treatment after adrenalectomy returned Gi and Gs close to control values. Go remained unaltered compared to controls but was 24% (n = 3) less than the adrenalectomized values (ANOVA; P less than 0.05). The levels of beta-subunit after dexamethasone replacement were significantly greater (ANOVA; P less than 0.05) than both the controls and adrenalectomized values. These results show that glucocorticoids can differentially regulate the amounts of G proteins in rat aorta as in other tissues. This may be an important mechanism by which steroids control receptor-G protein coupling and hence transmembrane signalling pathways in vascular smooth muscle.

Adrenalectomy↗
PubMed1990

Influence of pregnancy on G-protein coupling to adenylate cyclase activation in guinea-pig myometrium.

The regulatory factors controlling uterine activity during pregnancy remain unclear in many species. Since myometrial relaxants raise intracellular cyclic AMP, modulation of signalling pathways coupling cell-surface receptors to adenylate cyclase activation could be an important site for control. To assess the functional activity of the stimulatory GTP-binding protein Gs we have measured adenylate cyclase activation by GTP, its non-hydrolysable analogue guanosine 5'-(beta-gamma-imido)triphosphate (Gpp(NH)p), fluoride, forskolin and manganese in a 50,000 g membrane fraction prepared from the myometrium of non-pregnant, mid-pregnant (30-32 days) and late-pregnant (62-66 days) guinea-pigs (full term 67 +/- 2 days). While forskolin- and manganese-dependent enzyme activation was unaltered by pregnancy, maximal stimulation by Gpp(NH)p and fluoride was enhanced by up to 200%. Recovery of adenylate cyclase activity in the 50,000 g fraction was essentially constant at 20-24% of the total activity throughout pregnancy, and thus cannot explain the increases observed. Since guanine nucleotides and fluoride stimulate adenylate cyclase through activating Gs, and forskolin and manganese act at the level of the catalytic unit, these data are consistent with a pregnancy-related increase in Gs functional coupling while adenylate cyclase activity is unaltered. These observations suggest a physiological regulation of myometrial Gs activity during pregnancy which could facilitate hormonal stimulation of adenylate cyclase and contribute to uterine quiescence by increasing uterine sensitivity to relaxants.

Adenylyl Cyclases↗
PubMed1990

Studies on the growth of the fetal guinea pig. The effects of nutritional manipulation on prenatal growth and plasma somatomedin activity and insulin-like growth factor concentrations.

In guinea pigs between days 41-46 of pregnancy prenatal growth has been manipulated by alteration of nutritional state. Three methods were used. Uterine artery ligation at day 30 of pregnancy depressed fetal growth rate by greater than 50% and was associated with falls in plasma insulin, IGF-1, cortisol, thyroid hormone, glucose, acetate and free fatty acid concentrations and rises in that of IGF-2, glucagon and amino acids. Fetal plasma was inhibitory to sulphate incorporation into pig costal cartilage. Complete food withdrawal from pregnant guinea pigs for 2 days at days 43-44 of pregnancy caused mild fetal growth retardation and similar changes in plasma constituents, except in that plasma IGF-2 concentrations were now depressed and plasma was not inhibitory to sulphate incorporation into pig costal cartilage. Production of hypoglycaemia by 4-times-daily maternal injections of glucose between days 41-46 of pregnancy accelerated fetal growth rate. It also elevated fetal plasma concentrations of insulin, IGF-1, IGF-2, sulphation-promoting activity, thyroid hormones, glucose and free fatty acids and depressed that of glucagon and amino acids. Fetal growth rate during the experimental period showed a good correlation with plasma glucose, insulin and IGF-1 and, to a certain extent, with sulphation-promoting activity. It did not correlate closely with fetal plasma IGF-2 concentration. Hepatic glycogen concentrations showed a good correlation with plasma IGF-2 levels.

Amino Acids↗
PubMed1989

Adrenal responses to calcitonin gene-related peptide in conscious hypophysectomized calves.

1. Right adrenal and various cardiovascular responses to an intra-aortic infusion of calcitonin gene-related peptide (CGRP; 4 micrograms min-1) have been investigated in the presence and absence of exogenous adrenocorticotrophin ACTH1-24 (2 or 5 ng min-1 kg-1, I.V.). The adrenal clamp technique was employed in conscious calves in which the pituitary stalk had been cauterized 3-7 days previously. 2. At the higher dose (5 ng min-1 kg-1) the I.V. infusion of ACTH raised mean plasma ACTH concentration by about 1000 pg ml-1 and mean right adrenal cortisol output by about 750 ng min-1 kg-1. Under these conditions the intra-aortic infusion of CGRP had no apparent effect on adrenal cortisol output by about 750 ng min-1 kg-1. Under these conditions the intra-aortic infusion of CGRP had no apparent effect on adrenal function, other than to produce moderate adrenal vasodilatation. In contrast, in the absence of exogenous ACTH, the same dose of CGRP produced a substantial rise in cortisol output, which rose steadily to a peak mean value of 409 +/- 31 pg min-1 kg-1 at 10 min. It also significantly inhibited the release of free, but not of total, met5-enkephalin-like immunoreactivity from the gland (P less than 0.001) together with a significantly greater fall in adrenal vascular resistance (P less than 0.001). 3. At the lower dose of ACTH (2 ng min-1 kg-1, I.V.) CGRP raised mean plasma cortisol output from 314 +/- 31 to 486 +/- 44 ng min-1 kg-1 (P less than 0.01) and this effect was not attributable to an increase in the adrenal presentation rate of ACTH. 4. It is concluded that this peptide exerts a steroidogenic action on the adrenal cortex which is manifest in the absence of exogenous ACTH in the functionally hypophysectomized calf.

Adrenal Cortex↗
PubMed1989

Neuroendocrine responses to stimulation of the splanchnic nerves in bursts in conscious, adrenalectomized, weaned lambs.

1. Effects of stimulation of the peripheral ends of the splanchnic nerves below behavioural threshold at either 4 or 7 Hz continuously for 10 min, or at 40 or 70 Hz for 1 s at 10 s intervals for 10 min. have been compared in conscious adrenalectomized lambs. 2. Both patterns of stimulation resulted in an abrupt rise in mean aortic blood pressure of closely similar extent which was associated with reflex bradycardia. 3. At the lower frequencies both patterns of stimulation elicited a closely similar rise in mean plasma glucose, glucagon and pancreatic polypeptide concentration, but the fall in mean plasma insulin concentration was significantly greater during continuous stimulation. 4. Unlike other species in which the release of NPY and bombesin-like immunoreactivity (BLI) is potentiated by intermittent high-frequency stimulation, no significant differences were produced by changing the pattern of stimulation. The release of BLI was found to be frequency related over the ranges tested (4-7 Hz continuously and 40-70 Hz in bursts) whereas the release of NPY was not. 5. Splanchnic nerve stimulation also produced detectable rises in the mean plasma concentrations of noradrenaline and adrenaline. The mean average concentration of noradrenaline during stimulation in bursts was significantly higher than that during continuous stimulation (P less than 0.02). There was also a steady rise in mean plasma 3,4-dihydroxyphenylacetic acid (DOPAC) during stimulation followed by a further rise to significantly higher values (P less than 0.02) following stimulation in bursts at 40 Hz. 6. It is concluded that the pattern of stimulation is a less important determinant of autonomic responses to splanchnic nerve stimulation in sheep than in certain other species.

Adrenalectomy↗
PubMed1989

Adrenal responses to splanchnic nerve stimulation in conscious calves given naloxone.

1. The effects of stimulating the peripheral end of the right splanchnic nerve in the presence of naloxone (2 mg kg-1) have been investigated in conscious 3 to 6-week-old calves. 2. Mean aortic blood pressure rose to significantly higher levels during splanchnic stimulation in bursts at 40 Hz for 1 s at 10 s intervals than it did during stimulation at the corresponding continuous frequency (4 Hz). Furthermore, naloxone significantly reduced the fall in mean vascular resistance in response to both patterns of stimulation. 3. The output of catecholamines from the adrenal gland, together with the proportion of noradrenaline released, was significantly enhanced by stimulating the splanchnic nerves in bursts in animals pre-treated with naloxone and the proportion of noradrenaline released also increased. In both cases the output of adrenaline and noradrenaline was within the same range as that reported previously in normal control animals. 4. Naloxone significantly increased the amounts of enkephalin-like immunoreactivity and corticotrophin-releasing factor (CRF)-like immunoreactivity released from the adrenal gland in response to splanchnic nerve stimulation and raised the proportion of total to free met5-enkephalin that was secreted. 5. Naloxone also inhibited the rise in plasma adrenocorticotrophic hormone (ACTH) concentration during continuous stimulation at 4 Hz, but not during stimulation at 40 Hz in bursts. Under these latter conditions the output of cortisol apparently directly from the adrenal gland was inhibited. The finding that splanchnic nerve stimulation can potentiate the output of cortisol in response to ACTH was confirmed. 6. These results provide evidence that release of enkephalins and of CRF from the adrenal is inhibited by activating opioid receptors within the gland itself.

Adrenal Glands↗
PubMed1989

Myometrial alpha 1-adrenoceptors in pregnant guinea pig: their distribution and increased number.

There is evidence for an excitatory influence in pregnant and parturient myometrium mediated by alpha 1-adrenoceptors. Despite this there are no reports of direct measurement of changes in the density of these receptors throughout pregnancy. Indirect evidence could suggest a fall early in gestation followed by a sharp rise near term. Hence, to follow pregnancy-related changes, [3H]prazosin was employed in this study to measure alpha 1-adrenoceptors in guinea pig myometrium. High-affinity [3H]prazosin binding [dissociation constant (Kd) = 0.51 +/- 0.05 nM (n = 29)] displayed the pharmacological characteristics of alpha 1-adrenoceptors and yielded linear Scatchard plots, which in nonpregnant myometrium indicated a maximum binding density (Bmax) of 48.6 +/- 6.1 fmol/mg protein (n = 5). At all times during pregnancy alpha 1-adrenoceptor density was approximately 40% higher than the nonpregnant value. This, together with uterine growth, resulted in a progressive increase in total alpha 1-adrenoceptor population of up to 34-fold with a mean value of 7.54 +/- 2.26 pmol/uterus (n = 6) at term (67 +/- 2 days). This slow rise in receptor number does not suggest a major role in the processes triggering labour in this species. The distribution of alpha 1-adrenoceptors in tubal, perifetal, and cervical regions was similar in the 60-day pregnant uterus. As much of the uterus is not innervated at this time, a considerable proportion of these receptors are probably extrasynaptic.

Animals↗
PubMed1989

The effect of a 72-h fast on plasma levels of pituitary, adrenal, thyroid, pancreatic and gastrointestinal hormones in healthy men and women.

Seventeen human subjects fasted without electrolyte replacement for 3 days and hormone levels were measured before, during and after the fast. Immediate consequences of the fasting state in healthy human subjects include a marked increase in plasma cortisol. ACTH, beta-endorphin, beta-lipotrophic hormone, adrenaline, noradrenaline and dopamine. Levels of all these hormones were much greater on the first morning of the fast than in the post-prandial state, even though the plasma glucose level was no lower than that observed on the morning before the fast began. A clear fall in TSH and tri-iodothyronine (T3) levels was observed, but thyroxine levels did not change significantly. Insulin levels fell whereas proinsulin levels did not fall during the fast, though they did rise markedly upon re-feeding. An increase in GH levels was particularly apparent in male subjects, but was also seen in females when evening samples were compared. Pancreatic glucagon showed a modest rise during the fast, but fell again on refeeding; total glucagon also rose as the fast proceeded, but increased markedly upon re-feeding. Levels of gastrin and peptide YY remained low during the fast. Plasma electrolyte levels were unchanged. The following were closely correlated: cortisol with ACTH, T3 with log10 TSH, dopamine with noradrenaline, and (negatively, during the fast) pancreatic glucagon with glucose.

Adrenal Cortex Hormones↗
PubMed1989

Modulation of the responses of fetal sheep to adrenergic stimulation by adrenal demedullation and chemical sympathectomy.

The responses to sympathetic stimulation of fetal sheep adrenal-demedullated or sympathectomised by infusion of guanethidine sulphate have been studied. Sympathetic responses in such denervated or sympathectomised fetuses was studied by intravenous infusion of adrenaline or noradrenaline at about 0.4 micrograms/min per kg. This infusion increased plasma concentration 100-200 fold and there was no significant difference between the control fetuses and those in the vasrious treatment groups. Catecholamine infusions at these rates normally have little effect upon fetal blood gas and pH values, but in adrenal-demedullated fetuses adrenaline infusion drepressed fetal arterial PO2 by 4-6 mmHg (P less than 0.05). The heart rate and blood pressure responses to catecholamine infusion in sympathectomised fetuses was, as expected, much increased. Similar observations were made on adrenal-demedullated fetuses, an unexpected finding, and this is taken to illustrate loss of the adrenal medulla is associated with enhanced responsiveness to adrenergic stimulation in peripheral tissues. The majority of the endocrine and metabolic responses, as reflected in fetal plasma concentrations of ACTH, cortisol, insulin, glucose, lactate and fatty acids, to catecholamine infusion were similarly much enhanced by adrenal-demedullation and chemical sympathectomy. Of particular note was a substantial increase in the responsiveness of the fetal adrenal, as reflected in plasma cortisol, to stimulation by ACTH, a change that usually induces labour, but not so in the present sheep. The results on increased sensitivity in adrenal-demedullated fetuses are discussed in relation to likely tissue mechanisms mediating the changes.

Adrenal Glands↗
PubMed1989

Production of corticotrophin releasing hormone by the sheep placenta in vivo.

Corticotrophin-releasing hormone (CRH)-like activity has been reported in placental tissue and to rise sharply in maternal and fetal plasma during the third trimester of human pregnancy. It is unclear whether this applies to other species, if the placental secretes CRH, and if so what factors regulate its production. The present experiments were conducted on sheep 123-144 days pregnant. CRH-like activity was detected in the plasma of the uterine and umbilical vein at modest concentrations. These concentrations rose in the final days before delivery. Reduction of uterine blood flow, particularly caused by an elevation of maternal adrenaline, had the capacity to sharply increase placental output. The CRH-like activity on separation by hplc had the characteristics of 41CRH. The results are discussed in relation to the potential role of placentally-derived CRH.

Animals↗
PubMed1988

The adrenal contribution to the neuroendocrine responses to splanchnic nerve stimulation in conscious calves.

1. The extent to which the adrenal gland contributes to neuroendocrine responses to electrical stimulation of the peripheral end of the splanchnic nerve has been investigated in conscious calves in which the right nerve was stimulated either at 4 Hz continuously for 10 min or at 40 Hz in 1 s bursts at 10 s intervals for the same period. 2. It was confirmed that the release of neuropeptide Y (NPY) and of gastrin-releasing peptide (GRP) is potentiated by stimulation in bursts at a relatively high frequency and shown that the adrenal gland made a negligible contribution to these responses. 3. There was no detectable change in the concentration of vasoactive intestinal peptide (VIP) in the arterial plasma but the existence of a very small but highly significant rise in the output of VIP from the adrenal provided evidence that it was released within the gland in response to splanchnic nerve stimulation. 4. The concentration of calcitonin gene-related peptide (CGRP) in the arterial and adrenal venous effluent plasma was consistently below the level of detection of the assay. 5. Splanchnic nerve stimulation resulted in an abrupt rise in the output of both free and total met5-enkephalin-like immunoreactivity from the adrenal gland which was substantially potentiated by stimulating in bursts. This pattern of stimulation also increased the proportion released in a high-molecular-weight form. 6. Stimulation in bursts significantly enhanced the output of both adrenaline and noradrenaline from the adrenal and resulted in the release of proportionately more noradrenaline. Small amounts of dopamine and DOPAC were also released during splanchnic nerve stimulation and the output of dopamine was significantly increased by stimulating in bursts. 7. Both patterns of stimulation elicited an abrupt rise in mean plasma adrenocorticotrophic hormone (ACTH) concentration, which was associated with an increase in mean adrenal cortisol output and the former effect was significantly enhanced by stimulating in bursts. 8. It is concluded that certain responses to splanchnic nerve stimulation are significantly potentiated by an intermittent high-frequency pattern of stimulation, including all those that are attributable to adrenal medullary activity, whereas others are apparently unaffected by changes in stimulus pattern.

Adrenal Glands↗
PubMed1988

Secretion of corticotrophin releasing factor from the adrenal during splanchnic nerve stimulation in conscious calves.

1. The output of corticotrophin releasing factor-like immunoreactivity (CRF) from the adrenal gland has been investigated using the 'adrenal clamp' technique in conscious calves. 2. Stimulation of the peripheral end of the splanchnic nerve for 10 min increased the mean output of CRF progressively, so that it had risen by about twentyfold, to a peak incremental value of 24 +/- 4 pmol min-1 kg-1 at 10 min. This response was significantly increased by stimulating in bursts at 40 Hz for 1 s at 10 s intervals, which raised the mean CRF output by 44 +/- 7 pmol min-1 kg-1 at 10 min (P less than 0.05). 3. The mean output of adrenaline and noradrenaline rose more abruptly in response to splanchnic nerve stimulation with peak incremental values realized within 2.5 min. However, the ratios of adrenal CRF to catecholamine output were closely similar during the later stages of stimulation (7.5-10 min). There was a similarly abrupt rise in adrenal cortisol output in response to splanchnic nerve stimulation which was, nevertheless, linearly related to arterial plasma ACTH concentration throughout. 4. In hypophysectomized calves, administration of adrenocorticotrophic hormone (ACTH1-24) at a dose of 5 ng min-1 kg-1 reduced the output of adrenal CRF in response to splanchnic nerve stimulation by about 50% (P less than 0.05). 5. CRF isolated from adrenal venous effluent plasma, collected both at rest and during splanchnic nerve stimulation, was separated by reverse-phase high-pressure liquid chromatography and found to elute in a position identical to that of human 41CRF. This suggests that adrenal CRF is structurally closely similar to its pituitary counterpart.

Adrenal Glands↗
PubMed1988

A Mup promoter-thymidine kinase reporter gene shows relaxed tissue-specific expression and confers male sterility upon transgenic mice.

A hybrid gene was made by fusing the 2.2-kilobase 5' promoter region of a mouse group 1 major urinary protein (Mup) gene to the coding region of the herpes simplex virus type 1 thymidine kinase gene (HSV tk) and introduced into the genomes of mice by microinjection. Transgenic G0 males were sterile, or when fertile did not transmit the foreign gene, and the transgenic male descendants of G0 females were also sterile. Seven "lines" were established by breeding from G0 females and their transgenic female descendants. Six lines expressed HSV thymidine kinase activity in the liver, and activity correlated perfectly with the presence of HSV tk RNA. In three of four lines examined, expression was lower in female than in male liver, and in these lines the same sex difference was observed in the rate of run-on transcription of the foreign genes in liver nuclei. When females of one of the sexually dimorphic lines were treated with testosterone, the levels of HSV tk RNA and thymidine kinase activity were increased, although not to male levels. In these aspects of liver expression, and also in a lack of expression in seven other tissues, the hybrid gene exhibits many of the characteristics of an endogenous group 1 Mup gene. However, the gene was also expressed (at high levels) in the preputial gland and testis, two tissues in which Mup genes are not expressed. The gene, when introduced into five of the seven lines, carried a copy of the Escherichia coli supF gene attached beyond the 3' end of the HSV tk gene, but this did not affect the overall expression pattern. All of the lines were male sterile and expressed HSV thymidine kinase in the testis, but one line showed no activity in the liver, and another showed none in the preputial gland. Testicular expression is therefore the likely cause of sterility. Data are described which suggest that the causes of misexpression in the preputial gland and testis are different. Since expression in each tissue occurred in several lines, the structure of the hybrid gene must be responsible in each case. Five intensively studied lines showed at least four consistently different patterns of relative expression in preputial gland, testis, male liver, and female liver. These differences do not correlate in any way with the copy number of the foreign gene in the different lines and must be due to some other aspect of line specific integration.

Animals↗
PubMed1988

[3H]rauwolscine binding to myometrial alpha 2-adrenoceptors in pregnant guinea pig.

Uterine sympathetic nerves can exert an excitatory influence in late pregnancy and during parturition. Neuronal norepinephrine release is increased at these times and a diminished alpha 2-adrenoceptor-mediated prejunctional inhibition could account for this. To assess whether an altered receptor population may contribute, [3H]rauwolscine was used to measure alpha 2-adrenoceptors in myometrial membranes at time intervals throughout pregnancy. High affinity [3H]rauwolscine binding [Kd = 11.4 +/- 1.5 nM (n = 42)] yielded linear Scatchard plots that in nonpregnant myometrium indicated a maximum binding density (Bmax) of 217 +/- 42.4 fmol/mg protein. alpha 2-Adrenoceptor density was increased twofold at midpregnancy (31 days) and thereafter fell sharply by up to 90% toward term (67 +/- 2 days). When uterine growth is accounted for and data are expressed in terms of total myometrial population (uncorrected for plasma membrane recovery), alpha 2-adrenoceptor number was eightfold (midpregnancy) and fourfold (term) greater than the nonpregnant value of 804 +/- 322.4 fmol/uterus. alpha 2-Adrenoceptors were also found to bind dopamine with high affinity [Ki = 3.66 +/- 0.45 microM (n = 3)]. These observations could indicate a pregnancy-related change in uterine sympathetic autoinhibitory capacity and, since alpha 2-adrenoceptors appear also to be located postjunctionally, explain in part reports of altered myometrial responsiveness to norepinephrine infusion and also the uterotonic actions of dopamine.

Animals↗