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A McGregor

Publications and source records attributed to A McGregor.

At least 73 records · Page 4Linked to original sources
PubMed1995

Rapid desensitization of GnRH-stimulated intracellular signalling events in alpha T3-1 and HEK-293 cells expressing the GnRH receptor.

The gonadotropin-releasing hormone receptor (GnRH-R) desensitizes following chronic exposure to GnRH or its agonists. However, it is not certain whether the GnRH-R undergoes rapid homologous desensitization analogous to other members of the G-protein coupled receptor (GPCR) superfamily. This study investigated rapid desensitization events in two cell lines expressing the GnRH-R; (the pituitary gonadotrope alpha T3-1 cell line and the stably transfected human embryonal kidney cells, HEK-293). In both cell types, total inositol phosphate (IP) production did not desensitize, increasing linearly over 10 min. Short-term GnRH pretreatment also did not desensitize the rapid phase ( < or = sec) of the early Ins1,4,5P3 response despite a partial desensitization of the plateau phase ( > 1 min). It is likely that Ins1,4,5P3 metabolism rather than desensitization is responsible for this partial effect. In contrast, GnRH-stimulated calcium responses did desensitize in a dose-dependent fashion in both alpha T3-1 and HEK 293 cells expressing the GnRH-R. These results suggest that rapid GnRH-R desensitization occurs at a level beyond both the receptor and phospholipase C (PLC) activation. These events were receptor specific and not related to cell type, since similar rapid desensitization profiles were observed in both GnRH-R expressing pituitary and nonpituitary cell types. In contrast, profiles of GnRH-stimulated calcium responses were cell type specific.

Animals↗
PubMed1994

Identification of the vinculin-binding site in the cytoskeletal protein alpha-actinin.

Using low-speed sedimentation equilibrium we have established that vinculin binds to alpha-actinin with a Kd of 1.3 x 10(-5) M. Electron microscopy of negatively stained preparations of vinculin revealed spherical particles (diameter 11.2 nm; S.D. 1.7 nm, n = 21), whereas alpha-actinin appeared as a rod-shaped particle (length 33 nm; S.D. 3.3 nm, n = 23). Mixtures of the two proteins contained both 'lollipop'- and 'dumbell'-shaped particles which we interpret as either one or two spherical vinculin molecules associated with the ends of the alpha-actinin rod. We have further defined the vinculin-binding site in alpha-actinin using 125I-vinculin and a gel-blot assay in which proteolytic fragments of alpha-actinin and fragments of alpha-actinin expressed in Escherichia coli were resolved by SDS/PAGE and blotted to nitrocellulose. 125I-vinculin bound to polypeptides derived from the spectrin-like repeat region of alpha-actinin, but did not bind to the actin-binding domain. Binding was inhibited by a 100-fold molar excess of unlabelled vinculin. Using a series of glutathione S-transferase fusion proteins we have mapped the vinculin-binding site to a region toward the C-terminal end of the molecule (alpha-actinin residues 713-749). 125I-vinculin also bound to fusion proteins containing this sequence which had been immobilized on glutathione-agarose beads. The vinculin-binding site is localized in a highly conserved region of the molecule close to the first of two EF-hand calcium-binding motifs.

Actinin↗
PubMed1994

Effect of 6-hydroxydopamine lesions of the amygdala on intravenous cocaine self-administration under a progressive ratio schedule of reinforcement.

Bilateral six-hydroxydopamine (6-OHDA) lesions were placed in the amygdala of rats self-administering cocaine (1.5 mg/kg per injection i.v.) under a progressive ratio schedule of reinforcement. Post-lesion access to three doses of cocaine (1.5, 0.75 and 0.37 mg/kg per injection i.v.) revealed a lesion effect only at the highest dose. At this dose, the lesion caused a significant increase in breaking point. No change in the breaking point was produced at the lower two doses. The biochemical results show a significant reduction in dopamine and DOPAC levels within the amygdala and an increase in dopamine within the NACC. In contrast, noradrenaline and serotonin (5-HT) levels were unaffected by the lesion in any of the dissected areas. These results demonstrate that no specific effect on cocaine reinforcement was produced by 6-OHDA lesions of the amygdala. The possibility that the lesion may have attenuated the anxiogenic qualities of the high dose of cocaine is discussed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

The pathophysiology of the insulin-like growth factor axis in fetal growth failure: a basis for programming by undernutrition?

Recent evidence suggests that a number of adulthood conditions, including non-insulin dependent diabetes mellitus (NIDDM) and lipid and cardiovascular abnormalities are associated with intra-uterine growth retardation (IUGR). It is possible that this arises from programming of endocrine axes during development as a result of an adverse intra-uterine environment. Insulin-like growth factors (IGFs) are mitogenic polypeptides which stimulate cellular proliferation and differentiation and are important in human fetal development. The functions of IGFs are modulated by specific high affinity binding proteins (IGFBPs). IGFBP-1 is antagonistic to the insulin-like and growth promoting effects of IGF-I, and IGFBP-3 holds IGFs in the circulation by associating with IGFs and an acid labile subunit to form a ternary complex. Using specific radioimmunoassays and fetal serum obtained during diagnostic cordocentesis we have investigated the role of the IGF/IGFBP axis in human fetal development. In a study of 130 singleton pregnancies we have examined levels of immunoreactive IGFs and IGFBPs in normally grown fetuses (AGA), starved small fetuses affected by uteroplacental insufficiency (UPI), and non-starved small fetuses (SGA). IGF-I was significantly lower in the UPI group (n = 14, 7.8 +/- 0.6 micrograms l-1), than in either the SGA group (n = 22, 31.4 +/- 3.5 micrograms l-1, P = 0.0001) or the AGA group (n = 94, 36.3 +/- 1.9 micrograms l-1, P = 0.0001). IGFBP-3 showed similar changes (UPI: 682.6 +/- 50.0 micrograms l-1; SGA: 831.9 +/- 55.5 micrograms l-1; AGA: 847.7 +/- 19.8 micrograms l-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Carrier Proteins↗
PubMed1993

Dopaminergic antagonism within the nucleus accumbens or the amygdala produces differential effects on intravenous cocaine self-administration under fixed and progressive ratio schedules of reinforcement.

Bilateral intracerebral injections of the D1 receptor antagonist, SCH 23390, were administered into the nucleus accumbens (NACC) or amygdala (AMY) immediately prior to an i.v. cocaine self-administration session. Injection into both sites produced a dose-dependent (0.1-2.0 micrograms/injection) increase in the rate of cocaine self-administration under a fixed ratio (FR) schedule of reinforcement (1.5 mg/kg/injection). However, injection into the AMY produced a significantly greater increase in rate of drug intake than within the NACC. In contrast, under a progressive ratio (PR) schedule of cocaine reinforcement the D1 antagonist had very little effect within the AMY on break point (BP) but greatly reduced the BP following injection into the NACC. A locomotor activity study revealed that following systemic injection of cocaine (10 mg/kg i.p.), SCH 23390 (1.0 microgram/injection site) significantly reduced activity to comparable levels following injection into either brain site. This indicates that the dissociation of effects between the two neural sites within the cocaine self-administration paradigm does not appear to be due to greater locomotor reducing actions of the antagonist within the NACC. These results demonstrate that a significant contribution is made by AMY dopamine to cocaine reinforcement mechanisms, which appears to be different to that of the NACC. Moreover, they suggest that FR and PR schedules may measure different aspects of cocaine's CNS action which support self-administration behaviour.

Amygdala↗
PubMed1993

Another blood scandal?

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1993

L-tryptophan decreases the breaking point under a progressive ratio schedule of intravenous cocaine reinforcement in the rat.

L-Tryptophan (100 mg/kg, IP), the serotonin [5-hydroxytryptamine (5-HT)] amino acid precursor, significantly reduced the mean breaking point maintained under a self-administration progressive ratio schedule of IV cocaine reinforcement (0.6 mg/injection). This effect was produced over the 5 days of self-administration following treatment. Responding maintained under the same progressive ratio schedule for food reinforcement was not affected by L-tryptophan (100 mg/kg, IP). Rats administered L-tryptophan (100 mg/kg, IP) and denied access to cocaine on the day of treatment resumed normal self-administration patterns under a progressive ratio schedule on following test days. This indicates that L-tryptophan treatment alone did not induce long-term effects on cocaine self-administration. Thus, it would appear that the combination of this 5-HT manipulation and cocaine administration altered the reinforcing efficacy of the drug and induced a long-term decrement in breaking point under a progressive ratio schedule. This may have been due to an associative aversion to cocaine self-administration behaviour learned on the day of treatment and carried over to the subsequent 5 days of self-administration access.

Animals↗
PubMed1992

Differential effects of excitotoxic basolateral and corticomedial lesions of the amygdala on the behavioural and endocrine responses to either sexual or aggression-promoting stimuli in the male rat.

The effects of discrete excitotoxic lesions of the basolateral (BL) and corticomedial (CM) amygdaloid areas on both male rat sexual behaviour and inter-male agonistic behaviour were investigated. The effects of the same lesions on the hormonal responses (luteinising hormone (LH) following sexual behaviour, corticosterone following aggressive interactions) which accompany these behavioural responses were measured. Basolateral lesions had no effect on male sexual behaviour but significantly reduced the level of aggressive inter-male behaviour. However, the increase in plasma corticosterone concentration which occurs after such an interaction was not affected by basolateral lesions. In contrast, corticomedial lesions did not affect inter-male offence but severely affected copulatory behaviour, including a significant decrease in the males' investigation of the receptive female. However, the increase in plasma LH concentrations induced by the presence of a receptive female was not affected by the CM lesion. These results demonstrate a dissociation between the two amygdaloid regions with respect to the contributions made to the two social behaviours under study. This anatomical division may reflect differential amygdaloid sensory control of these behaviours. A further dissociation between amygdaloid contribution to behavioural and hormonal responses was also revealed. Neither hormonal response showed a parallel decline with the relevant behavioural response, suggesting that neither the basolateral nor corticomedial amygdaloid complex is responsible for coordinating behavioural and endocrine responses to a specific stimulus.

Agonistic Behavior↗
PubMed1992

Specific effects of beta-endorphin infused into the amygdala on sexual behaviour in the male rat.

Bilateral intra-amygdaloid infusions of 0, 20, 60, 120 and 200 pmol beta-endorphin were administered to sexually experienced male rats in a Latin-square design. Sixty, 120 and 200 pmol beta-endorphin significantly decreased preintromission investigation rate and increased intromission latency with an oestrous female. No other effects on the male rats' sexual behaviour were produced. beta-Endorphin-induced effects on preintromission investigation and intromission latency were naloxone reversible (5 mg/kg, i.p.). Similar doses of intra-amygdaloid beta-endorphin had no effect on aggressive interaction with another, strange, male behaviour and similar doses of intra-amygdaloid corticotropin-releasing factor had no effect on sexual behaviour. Thus, there was both behavioural and chemical specificity of intra-amygdaloid beta-endorphin-induced effects on male sexual behaviour. Bilateral 60 pmol beta-endorphin infusions into the caudate-putamen had no effects on male sexual behaviour, demonstrating anatomical specificity of the intra-amygdaloid-induced effects. Basolateral excitotoxic lesions did not prevent the behavioural effects of intra-amygdaloid beta-endorphin infusions. These results demonstrate that intra-amygdaloid beta-endorphin specifically suppresses the precopulatory phase of male rat sexual behaviour but leaves the execution of the copulatory series intact once it has been initiated. This effect appears to be mediated via the corticomedial amygdaloid region. The change in precopulatory behaviour suggests that beta-endorphin may interfere with the processing of sensory information from the female, thus delaying appropriate initiation of the copulatory series.

Aggression↗
PubMed1992

The effects of beta-endorphin infusions into the amygdala on visual and olfactory sensory processing during sexual behaviour in the male rat.

Sexually experienced male rats infused bilaterally into the amygdala with 60 pmol beta-endorphin show decreased rate of precopulatory investigation of the female and delayed intromission latency, but copulation is left unaltered. Such males are still able to discriminate between the odours of bedding from receptive and unreceptive females, demonstrating that beta-endorphin does not impair the ability to detect sexually relevant odours. Preventing visual cues emitted by females during proceptive behaviour (by treating them with haloperidol) delayed intromission latency but had no effect on preintromission investigation. Intra-amygdaloid beta-endorphin exacerbated the effects of this treatment on the intromission latency. Inducing anosmia in males (by applying zinc sulphate solution to the olfactory mucosa) decreased their anogenital investigation and delayed their intromission latency. These effects were not enhanced by intra-amygdaloid beta-endorphin. Allowing males to investigate and initiate the first intromission prior to intra-amygdaloid infusion had no effects on subsequent intromissions. However, if following an intromission with one female and an infusion of beta-endorphin, the male was presented with an unfamiliar female then the effects of intra-amygdaloid beta-endorphin on investigation and intromission returned. These results suggest that beta-endorphin in the amygdala interferes with the processing of female-specific olfactory information. Without this processed information, classification of the female as a sexual stimulus may be impeded and thus sexual arousal delayed.

Amygdala↗
PubMed1992

Potential oxyradical damage and energy status in individual muscle fibres from degenerating muscle diseases.

Inherited degenerating muscle diseases result in disintegration of muscle fibres, which is initiated by a lack of or alteration to a muscle protein. In Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) the protein is known to be dystrophin. The cellular function of dystrophin is not known in any detail but its absence appears to lead to a weakening of the sarcolemma. It has been proposed by Murphy and Kehrer that this leads ultimately to increased oxyradical production which may accelerate the degeneration. Studies have been carried out on individual muscle fibres derived from biopsy samples from patients with a number of degenerative muscle diseases. The glutathione cycling components, in particular glutathione and glutathione peroxidase, are significantly elevated in DMD, BMD and other diseases. Glutathione reductase is also elevated in some of these diseases. Energy producing systems are also affected particularly in intact fibres of muscle derived from muscle at an advanced stage of the disease. These results suggest that oxyradical damage may occur as a secondary consequence of muscle degenerating disease, leading to a breakdown in the glycogenolytic energy producing system.

Adenosine Diphosphate↗
PubMed1991

Insidious loss of renal function in patients with anticardiolipin antibodies and absence of overt nephritis.

Circulating anticardiolipin antibodies are associated with recurrent thrombosis, fetal loss and thrombocytopenia. We have identified four patients with SLE or lupus-like disease who have high circulating levels of ACLA, repeated thrombosis and evidence of renal disease. Their clinical signs and symptoms of lupus activity were minimal, yet all had renal insufficiency with GFR 50 ml/min or less despite no history nor evidence of overt nephritis (proteinuria less than 0.5 g/day and no haematuria). Renal biopsy specimens showed focal ischaemic lesions with no evidence of active lupus nephritis. We describe a new lesion of renal ischaemia secondary to non-inflammatory vascular pathology associated with circulating ACLA.

Adult↗