Reliability and validity of the Self-Reflection and Insight Scale for psychologists and the development and validation of the revised short version.

Self-reflection is broadly considered a core competency for psychologists; however, there is an absence of measures of self-reflection, limiting the extent to which self-reflection can be assessed in both research and practice contexts. Whilst the Self-Reflection and Insight Scale (Grant et al., 2002) has been validated in a range of formats with different populations, it has not yet been validated with psychologists. Further, the psychometric properties of a short version of the scale (Silvia, 2021) have not been examined for use with psychologists. This study tested the factor structure, internal consistency and convergent and divergent validity of the Self-Reflection and Insight Scale with registered psychologists (N = 123), finding both the full scale and short version to have sound psychometrics. However, as there were low loading items across both versions of the measure, and the short version also excluded high-loading items, the SRIS-Revised (SRIS-R) was formed through model improvement, retaining a total of 14 items. This revised version of the scale captures high loading items without redundancy of low-loading items, resulting in a measure that parsimoniously captures the construct of self-reflection as relevant to psychologists. The SRIS-R demonstrated good internal consistency (α = .882), convergent, divergent and construct validity. Scores on the SRIS-R were used to test whether there was a correlation between self-reflection and years of professional registration, with this not being significant.

Efficacy of single-dose intravenous phenylbutazone and flunixin meglumine before, during and after exercise in an experimental reversible model of foot lameness in horses.

REASONS FOR PERFORMING STUDY: Objective blinded efficacy data during exercise are lacking on the use of single-dose i.v. nonsteroidal anti-inflammatory drugs (NSAIDs) before, during and after exercise. HYPOTHESIS: Single i.v. doses of either phenylbutazone (PBZ) or flunixin meglumine (FM) would prove more efficacious than negative saline control (SAL) before, during and after exercise in a reversible model of foot lameness. METHODS: Six Quarter Horse mares had lameness induced by tightening a set screw against a heart bar shoe 1 h prior to treatment. Randomised blinded treatments included PBZ (4.4 mg/kg bwt i.v.), FM (1.1 mg/kg bwt i.v.), and SAL (1 ml/45 kg i.v.). Heart rate and lameness score (LS) were recorded at rest; every 20 min after lameness induction for 5 h and at the end of 2 min treadmill workloads of 2 and 4 m/s. Heart rate was also recorded from 0.5-60 min post exercise. Results were compared using RM ANOVA and Student-Newman-Keul's test (HR) and Wilcoxon signed rank test (%ΔLS) with significance set at P < 0.05. RESULTS: Pre-exercise mean HR was decreased for both NSAIDs compared to SAL from 1:20-4 h post treatment (P < 0.05). Pre-exercise mean %ΔLS was decreased for PBZ (1:20-4 h) and FM (1-4 h) compared to SAL (P < 0.01). With exercise, there were no HR differences between treatments (P > 0.05), but mean %ΔLS was decreased for both NSAIDs compared to SAL (P < 0.01). Mean recovery HR was decreased for PBZ and FM from 1-60 min compared to SAL (P < 0.05). CONCLUSIONS: PBZ and FM demonstrated definitive clinical efficacy after single i.v. doses before, during and after exercise. Use of single i.v. doses during competition may mask lameness and may affect the ability of judges in determining the soundness of horses in competition.

Proteome-based plasma biomarkers for Alzheimer's disease.

Alzheimer's disease is a common and devastating disease for which there is no readily available biomarker to aid diagnosis or to monitor disease progression. Biomarkers have been sought in CSF but no previous study has used two-dimensional gel electrophoresis coupled with mass spectrometry to seek biomarkers in peripheral tissue. We performed a case-control study of plasma using this proteomics approach to identify proteins that differ in the disease state relative to aged controls. For discovery-phase proteomics analysis, 50 people with Alzheimer's dementia were recruited through secondary services and 50 normal elderly controls through primary care. For validation purposes a total of 511 subjects with Alzheimer's disease and other neurodegenerative diseases and normal elderly controls were examined. Image analysis of the protein distribution of the gels alone identifies disease cases with 56% sensitivity and 80% specificity. Mass spectrometric analysis of the changes observed in two-dimensional electrophoresis identified a number of proteins previously implicated in the disease pathology, including complement factor H (CFH) precursor and alpha-2-macroglobulin (alpha-2M). Using semi-quantitative immunoblotting, the elevation of CFH and alpha-2M was shown to be specific for Alzheimer's disease and to correlate with disease severity although alternative assays would be necessary to improve sensitivity and specificity. These findings suggest that blood may be a rich source for biomarkers of Alzheimer's disease and that CFH, together with other proteins such as alpha-2M may be a specific markers of this illness.

Expression of the Fe65 adapter protein in adult and developing mouse brain.

Fe65 is a multimodular adaptor protein expressed mainly in the nervous system. Fe65 binds to the Alzheimer's disease amyloid precursor protein (APP) and the interaction is mediated via a phosphotyrosine binding domain in Fe65 and the carboxy-terminal cytoplasmic domain of APP. Fe65 modulates trafficking and processing of APP, including production of the beta-amyloid peptide that is believed to be central to the pathogenesis of Alzheimer's disease. Fe65 also facilitates translocation of a carboxy-terminal fragment of APP to the nucleus and is required for APP-mediated transcription events. In addition, Fe65 functions in regulation of the actin cytoskeleton and cell movement. Here we report the distribution profile of Fe65 immunoreactivity in adult mouse brain. Fe65 expression was found to be widespread in neurones in adult brain. The areas of highest expression included regions of the hippocampus in which the earliest abnormalities of Alzheimer's disease are detectable. Fe65 was also highly expressed in the cerebellum, thalamus and selected brain stem nuclei. Fe65 was evident in a sub-set of astrocytes within the stratum oriens and radiatum in the hippocampus. Expression of Fe65 was found to be developmentally regulated with levels reducing after embryonic day 15 and increasing again progressively from post-partum day 10 up to adulthood, a developmental pattern that partially parallels that of APP. These data indicate a widespread distribution of Fe65 in neurones throughout mouse brain and also suggest that Fe65 may have functions independent of APP and any potential role in the pathogenesis of Alzheimer's disease.

The expression of the glutamate re-uptake transporter excitatory amino acid transporter 1 (EAAT1) in the normal human CNS and in motor neurone disease: an immunohistochemical study.

A monoclonal antibody to excitatory amino acid transporter 1 (EAAT1) has been generated which robustly stains paraffin-embedded, formaldehyde-fixed as well as snap-frozen human post-mortem brain tissue. We have used this antibody to map the distribution of EAAT1 throughout normal human CNS tissue. In addition this antibody has been used to perform a semi-quantitative immunohistochemical analysis of the expression of EAAT1 in motor cortex and cervical cord tissue taken from motor neurone disease cases (n=17) and neurologically normal controls (n=12). By comparing the relative optical density measurements of identical regions of motor cortex and cervical spinal cord an increase in the expression levels of EAAT1 was observed in motor neurone disease tissue compared to the control tissue and in both motor cortex and cervical spinal cord (9-17% and 13-33% increases respectively). EAAT1 was observed to be the most abundant transporter in more "caudal" brain regions such as the diencephalon and brainstem and its expression in other regions was frequently more uniform than that of EAAT2. In the motor cortex, EAAT1 immunoreactivity was present in all grey matter laminae, with some staining of individual astrocytes in the white matter. In spinal cord, EAAT1 immunoreactivity was strongest in the substantia gelatinosa. In the ventral horn, motor neurones were surrounded with a dense rim of perisomatic EAAT1 immunoreactivity, and the neuropil showed diffuse staining. Additional studies using double-labelling immunocytochemistry demonstrated that astrocytic co-localisation of EAAT1 and EAAT2 may occasionally be seen, but was not widespread in the human CNS and that in general astrocytes were positive for either EAAT1 or EAAT2. These results demonstrate that the EAAT1 has a widespread abundance throughout all regions of the human CNS examined and that there exist discrete populations of astrocytes that are positive solely for either EAAT1 or EAAT2. Furthermore, there is evidence to suggest that altered EAAT1 expression in motor neurone disease follows a different pattern to the reported changes of EAAT2 expression in this condition, indicating that the role of glutamate transporters in the pathogenesis of motor neurone disease appears more complex than previously appreciated.

Mutation screening of manganese superoxide dismutase in amyotrophic lateral sclerosis.

Seventy-seven cases of ALS were screened for mutations in the manganese superoxide dismutase gene (SOD2). DNA was extracted from CNS tissue and screened using single stranded conformation polymorphism and heteroduplex analysis. No mutations were identified in the entire coding region of the SOD2 gene. The known polymorphism in the mitochondrial targeting sequence was identified. No association was found between this polymorphism and ALS. A further polymorphism was detected in the intronic sequence upstream of exon 4, though no association with ALS was demonstrated. We therefore conclude that mutations in SOD2 do not appear to cause ALS.

Screening of AP endonuclease as a candidate gene for amyotrophic lateral sclerosis (ALS).

DNA extracted from CNS tissue of 84 patients was screened by single-stranded conformation polymorphism (SSCP) and heteroduplex analysis for mutations in the apurinic/apyrimidinic endonuclease (APE) gene. One mutation was identified and characterized as a 4bp deletion in the 3'UTR. A rare polymorphism was identified in exon 3 and a common polymorphism in the coding region of exon 5. These results suggest that APE mutations do not account for a large number of ALS cases.

Thermal, but not mechanical, nociceptive behavior is altered in the Zucker Diabetic Fatty rat and is independent of glycemic status.

This study investigated the possible link between developing hyperglycemia and mechanical and/or thermal hyperalgesia in the Zucker Diabetic Fatty (ZDF) rat. When normoglycemic (nonfasting blood glucose levels of 6 mM), 6-week-old ZDF rats were glucose intolerant compared to the nondiabetic Zucker lean control (ZL) rats, but there was no difference in their response to a noxious mechanical (paw pressure test) or thermal (hot plate) stimulus (mechanical nociceptive thresholds: ZDF 176.7+/-14.4 g, ZL 161.7+/-13.3 g; latencies to response to the thermal stimulus: ZDF 13.1+/-1.6 sec, ZL 16.7+/-1.5 sec). Blood glucose levels in untreated ZDF rats increased to 28.4+/-2.9 mM by 20 weeks of age, while ZDF rats treated with the insulin sensitizer, rosiglitazone, and ZL rats remained normoglycemic (< or =8 mM) throughout the study. Hyperglycaemia in ZDF rats was not associated with mechanical hyperalgesia, as the nociceptive threshold remained constant in both the rosiglitazone-treated and untreated ZDF rats and in the ZL rats throughout the study. In contrast, the latency to response to the thermal stimulus increased with time in ZL rats, but remained constant in hyperglycaemic ZDF rats such that the difference reached significance by 9 weeks of age (ZDF 11.6+/-1.7 sec, ZL 21.8+/-2.7 sec, p<0.01) and is consistent with hyperalgesia in the ZDF phenotype. However, this difference was not moderated by maintaining normoglycaemia in rosiglitazone-treated ZDF rats (12.8+/-1.3 sec). Together, the data suggest that hyperglycemia does not play a central role in the development of hyperalgesia in the ZDF rat.

5-HT4 receptor antagonism potentiates inhibition of intestinal allodynia by 5-HT3 receptor antagonism in conscious rats.

Acute levels of distension were applied by balloon to the colo-rectal region in conscious rats and visceromotor responses observed as abdominal muscle contraction; the threshold was typically between 10-40 mmHg. In saline-pretreated rats, the selective 5-HT3 (granisetron) and 5-HT4 (SB-207266) receptor antagonists had no effects on the visceromotor thresholds. 5-Hydroxytryptophan 10 mg/kg, subcutaneously (s.c.) decreased the distension threshold, indicating mechanical allodynia. This increased sensitivity was dose-dependently inhibited by granisetron but was unaffected by SB-207266 100 microg/kg, s.c., a dose which maximally and selectively antagonizes at 5-HT4 receptors. However, this dose of SB-207266 potentiated the inhibitory activity of submaximally-effective doses of granisetron, reducing the ED50 from 0.83 to 0.02 microg/kg, s.c., but without changing the maximum response or the bell-shaped nature of the dose-response curve for granisetron. These data suggest that 5-HT4 receptor activation enhances the ability of 5-HT3 receptor activation to induce intestinal allodynia.

The expression of the glial glutamate transporter protein EAAT2 in motor neuron disease: an immunohistochemical study.

Emerging evidence suggests that a disturbance of the glutamate neurotransmitter system may be a contributory factor to motor neuron injury in motor neuron disease. Previous autoradiographic and immunoblotting studies have suggested that there may be reduced expression of glutamate transporter proteins in pathologically affected areas of the CNS in motor neuron disease. This study further explores the possible alteration in expression of the excitatory amino acid transporter protein EAAT2 in MND, by examining the protein expression in situ, in frozen sections, using immunohistochemistry. The aim of the study was to compare the distribution and density of EAAT2 in the motor cortex and spinal cord of MND cases (n = 16) compared with neurologically normal controls (n = 12), matched for relevant parameters. A novel, previously characterized, monoclonal antibody to EAAT2 was employed. EAAT2 immunoreactivity in motor neuron disease and control cases was compared using relative optical density measurements generated by computerized image analysis. In the motor cortex, EAAT2 immunoreactivity was laminated comprising a superficial intense band (corresponding to layers 1 and 2); a paler middle band (layer 3 and part of 5) and a more intense deep layer (layers 5 and 6). In the spinal cord, the ventral horn showed strong immunoreactivity with dense perisomatic staining around motor neuron cell bodies, the substantia gelatinosa showed moderate diffuse staining and the intermediate spinal laminae showed weak staining. This general pattern of immunoreactivity was preserved in the motor neuron disease cases. However, in the motor neuron disease cases compared with controls, the optical density values for EAAT2 immunoreactivity were significantly reduced in all grey matter regions of the lumbar spinal cord (P < 0.001) and were increased in the middle laminae of the motor cortex (P < 0.05). This study indicates that glutamate transporter pathology in motor neuron disease may be a more complex phenomenon than previously recognized.

SB-207266: 5-HT4 receptor antagonism in human isolated gut and prevention of 5-HT-evoked sensitization of peristalsis and increased defaecation in animal models.

SB-207266 is a new 5-HT4 receptor antagonist which in a pilot study reduced the symptoms of irritable bowel syndrome. To help validate this and further studies, we examined the ability of SB-207266 to antagonize at the human 5-HT4 receptor (human isolated intestine) and to affect the mechanisms of peristalsis (guinea-pig isolated ileum) and defaecation (conscious, fed mice). In the human intestine, the potency of 5-HT4 receptor antagonism (pKB 9.98) was similar to that previously demonstrated using a guinea-pig model of the receptor, validating the use of SB-207266 in clinical trials. In each of the animal models, SB-207266 did not affect normal patterns of intestinal motility measured in the absence of exogenous 5-HT. However, SB-207266 10-1000 pM concentration-dependently antagonized the ability of 5-HT (0.1 microM) to sensitize the peristaltic reflex and lower the distension threshold at which peristalsis was evoked. In mice, oral or subcutaneous (s.c.) doses of SB-207266 dose-dependently prevented the ability of the 5-HT precursor, 5-hydroxytryptophan (5-HTP, 10 mg kg-1 s.c.) to increase both the rate of defaecation of formed faecal pellets and their fluid content. SB-207266 was maximally active at 10 micrograms kg-1 s.c. and 1000 micrograms kg-1 p.o. SB-207266 may therefore represent a new class of therapeutic agent, capable of preventing the actions of an important sensitizer of gut function.

Nucleoside diphosphate kinase and Cl(-)-sensitive protein phosphorylation in apical membranes from ovine airway epithelium.

We have previously shown that nucleotide species (adenosine triphosphate [ATP] or guanosine triphosphate [GTP]), [Cl-], and anion species determine the steady-state phosphorylation of apical membrane proteins within human airway epithelium in vitro. We found that a Cl(-)-regulated 37-kD protein (p37) principally phosphorylated with GTP but not ATP as substrate. Here we show that apical membranes from sheep tracheal epithelium also contain a Cl(-)-regulated 37-kD phosphoprotein (p37s) and characterize one of the kinases involved in the regulation of p37s. Analysis of phosphorylation of apical membrane proteins with gamma[32P]GTP in the presence of MgCl2 showed that two proteins circa 19 and 21 kD (p19s and p21s) were transiently phosphorylated before p37s. Renaturation of apical membrane proteins within polyacrylamide gels showed that p19s and p21s autophosphorylated with either gamma[32P]GTP or gamma[32P]ATP as substrates, suggesting that the two proteins were kinases. Immunoblotting and immunoprecipitation with a specific polyclonal antibody showed that p21s was a membrane-bound isoform of nucleoside diphosphate kinase (NDPK, EC 2.7.4.6), a protein kinase which catalyzes transfer of terminal phosphate from ATP to diphosphate nucleotides and is, among other functions, essential for cell secretion. Incubation of apical membrane proteins in the presence of gamma[32P]ATP and guanosine diphosphate (GDP) (but not GDPbetaS) resulted in enhancement of phosphorylation of p37s. Dephosphorylation of NDPK was stimulated by the addition of Mg2+, Mn2+, and Co2+ (but not Zn2+ or Ca2+). Our data show that ovine trachea is a good model for further characterization of the chloride-dependent cascade in airway epithelium.

Changing the transition--the Canadian experience.

Ms Banner suggested that her role after the previous two lively and controversial presentations was to calm everyone down and present an alternative that delegates might quietly contemplate. She introduced herself as the executive director of the Canadian resident matching service, an organization that sits in the middle of all the medical education organizations in Canada and which in a way acts as an archive to the kind of changes that have been going on for the last 5-7 years. Much of what the two previous speakers discussed are the reasons why Canada is where it is today, and why it has taken the steps that it did. This paper describes the context of the transition from student to practising doctor in Canada, the pressures for change in this pre-registration period, the impact change has had on medical education and continuing challenges.

Expression of the glial glutamate transporter EAAT2 in the human CNS: an immunohistochemical study.

Glutamate transporters play an essential role in terminating the excitatory glutamatergic signal at post-synaptic receptors and in protecting neurones from excitotoxic effects, as well as replenishing the neurotransmitter supply at glutamatergic synapses. The distribution and density of glutamate transporters may be important determinants of vulnerability to glutamate-mediated injury. There is emerging evidence that glutamate transporter dysfunction may be present in motor neurone disease (MND). In this study, a monoclonal antibody, suitable for immunohistochemistry (IHC) in human post-mortem tissue, was produced to the human astrocytic glutamate transporter EAAT2 (excitatory amino acid transporter 2). Western blotting of homogenates of human cortical tissue with the EAAT2 antibody produced a discrete band at 66 kDa. Detailed IHC analysis of the expression of the EAAT2 protein in the human CNS was undertaken. EAAT2 was exclusively localised to astrocytes, with preferential expression in the caudate nucleus, nucleus basalis of Meynert, spinal ventral horn, cerebral cortex and hippocampus, but with lower levels of expression throughout many other CNS regions. Motor neurone groups vulnerable to neurodegeneration in MND appeared distinctive in being surrounded by extensive, coarse, strongly immunoreactive perisomatic glial profiles. Motor neurone groups which tend to be spared in MND, such as those present in the oculomotor nucleus, showed a lower expression of EAAT2, with fewer perisomatic profiles. The EAAT2 antibody will provide a useful tool for increasing our understanding of the role of EAAT2 in excitatory neurotransmission in health and disease states.

Increased defaecation caused by 5-HT4 receptor activation in the mouse.

The precursor to 5-hydroxytryptamine (5-HT), 5-hydroxytryptophan, (5-HTP, 5-50 mg.kg-1) administered subcutaneously (s.c.) to conscious, fed mice caused a dose dependent increase in faecal pellet and fluid output. To avoid provoking watery diarrhoea, all experiments were performed using 5-HTP at 10 mg.kg-1. This dose caused maximal increases in the fluid content (471 +/- 41%) and number of formed faecal pellets defaecated (328 +/- 13% n = 25), 10 and 20 min respectively after administration, when compared to saline-treated mice. In both saline- and 5-HTP-treated mice methiothepin, ketanserin, mianserin and granisetron reduced defaecation at high s.c. doses (100 micrograms.kg-1 or 1000 micrograms.kg-1). The 5-HT4 receptor antagonists, DAU 6285 (endo-6-methoxy-8-methyl-8-azabicyclo[3.2.1]oct-3-yl-2,3-dihydro-2-oxo-1 H-benzimidazole-1-carboxylate hydrochloride), SDZ 205-557 (2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino) ethyl ester) and SB 204070 ([1-butyl-4-piperidinylmethyl]-8-amino-7-chloro-1,4-benzodioxan -5- carboxylate), had no effects when administered s.c. to saline-treated mice, but dose-dependently inhibited the 5-HTP-evoked responses. Only SB 204070 at 1000 micrograms.kg-1 completely inhibited the responses to 5-HTP returning them to normal levels. We conclude that SB 204070 is a potent antagonist for the investigation of 5-HT4 receptor function in both normal and disturbed gastrointestinal activity.

5-Hydroxytryptamine3 receptor antagonism modulates a noxious visceral pseudoaffective reflex.

5-Hydroxytryptamine (5-HT) receptor agonists and antagonists were dosed intravenously (i.v.) and studied for their effects on the depressor cardiovascular pseudoaffective reflex evoked by acute noxious colo-rectal distension in the anaesthetized rat. Methiothepin (100 micrograms kg-1) caused an initial, unsustained blockade of evoked depressor responses whilst ketanserin (100 micrograms kg-1) was without effect. By comparison, ondansetron dose dependently inhibited evoked depressor responses and was maximally active at 100 micrograms kg-1, causing a 57.5 +/- 0.9% reduction. An ID50 value of 36.7 micrograms kg-1 was estimated by regression analysis. In contrast, granisetron caused complete blockade of the depressor response with an ID50 of 0.4 microgram kg-1. Bell-shaped dose-effect curves were demonstrated for both granisetron and ondansetron. Intrathecal dosing with granisetron (100 ng) into the thoracolumbar region of the spinal cord prevented the depressor response to colo-rectal distension, suggesting a spinal site of action. The pseudoaffective depressor responses were not facilitated by pre-dosing with the 5-HT receptor agonists, 8-OH DPAT, alpha-methyltryptamine or 1-phenyl-biguanide. However, 8-OH DPAT (100 micrograms kg-1) facilitated pressor responses. It is suggested that 5-HT3-like receptors may have a role in modulating depressor responses to visceral pain and that in this action different 5-HT3 receptor antagonists are not necessarily equi-effective.

Differences between 5-HT3 receptor antagonists in modulation of visceral hypersensitivity.

1. Noxious colo-rectal distension was applied in conscious rats by acute balloon inflation and the effects observed as abdominal muscle contraction with the threshold typically between 10-40 mmHg. The effects of 5-HT3 receptor antagonists on responses to noxious colo-rectal distension were then studied in both normal rats and those pretreated with 5-hydroxytryptophan (5-HTP). 2. Granisetron and ondansetron (10 micrograms kg-1 and 1 mg kg-1, s.c.) had no effect on visceromotor thresholds to colo-rectal distension in normal rats. 3. Hypersensitivity of the colo-rectum was achieved by systemic administration of a low dose of 5-HTP (10 mg kg-1, s.c.) which lowered the distension pressure required to induce the visceromotor reflex; analysis of variance showed a highly significant treatment effect (F1,11 = 84.26, P < 0.001). 4. Granisetron, zatosetron, bemesetron and renzapride equi-potently increased the threshold values at which distension evoked a visceromotor reflex after dosing with 5-HTP, with a maximal response 3.6 to 4.2 fold above saline controls, at 10 micrograms kg-1, s.c. Metoclopramide (10 micrograms kg-1) also raised the level of distension required to elicit a response. By comparison, tropisetron caused a small, non-significant increase in visceromotor threshold values and only at high doses (1 mg kg-1), whilst ondansetron and BRL 46470 had no significant effects at doses up to 10 mg kg-1. 5. The response to granisetron (10 micrograms kg-1, s.c.) in 5-HTP-treated rats was unaltered by pre-administration of naloxone (5 mg kg-1, s.c.). 6. These results suggest that a 5-HT3-like receptor modulates 5-HTP- evoked visceral hypersensitivity.However, the rank order of antagonist potency does not correlate with their order of potency against the classically defined 5-HT3 receptor.

Effects of FMRFamide-related peptides and morphine on the isolated foregut of the locust Schistocerca gregaria.

1. Morphine and YAGFMamide were the most effective potentiators of 5-hydroxytryptamine (5-HT)-induced relaxation of the isolated foregut. 2. Morphine had no effect on proctolin-induced tissue contraction which was inhibited by YGGFMamide and YFMRFamide. 3. The differing potency of FaRPs and morphine to potentiate 5-HT effects and reduce proctolin responses suggests that there are two separate FaRP receptor sub types. 4. This proposal is supported by the observation that, while naloxone (10(-5) M) is a relatively potent antagonist of FaRP induced inhibition of proctolin contraction, it has less effect on FaRP-induced potentiation of 5-HT-induced relaxation.

Tyramine antagonizes proctolin-induced contraction of the isolated foregut of the locust Schistocerca gregaria by an interaction with octopamine2 receptors.

1. Octopamine (OA) (10(-7)-10(-5) M) relaxed isolated foreguts. Tyramine mimicked the effects of OA but was 64x less potent. 2. Proctolin (10(-8) M to 10(-6) M) induced contraction of isolated foreguts was antagonised non competitively by tyramine. 3. Mianserin (10(-6) M) was a non competitive antagonist of relaxation caused by tyramine but was without effect on proctolin induced contraction. 4. Caffeine (1 microM and 2 microM) caused non competitive inhibition of proctolin-induced tissue contraction. 5. It is concluded that tyramine antagonises proctolin-induced contraction of the foregut by activating an adenylate cyclase-linked OA2 receptor.