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D A Hall

Publications and source records attributed to D A Hall.

At least 37 records · Page 2Linked to original sources
PubMed2000

Modulation and task effects in auditory processing measured using fMRI.

Active listening has been reported to elicit a different sensory response from passive listening and is generally observed as an increase in the magnitude of activation. Sensory activation differences may therefore be masked by the effect of attention. The present study measured activation induced by static and modulated tones, while controlling attention by using target-discrimination and passive listening tasks. The factorial design enabled us to determine whether the stimulus-induced activation in auditory cortex was independent of the information-processing demands of the task. Contrasted against a silent baseline, listening to the tones induced widespread activation in the temporal cortex, including Heschl's gyrus (HG), planum temporale, superior temporal gyrus (STG), and superior temporal sulcus. No additional auditory areas were recruited in the response to modulated tones compared to static tones, but there was an increase in the response in the STG, anterior to HG. Relative to passive listening, the active task increased the response in the STG, posterior to HG. The active task also recruited regions in the frontal and parietal cortex and subcortical areas. These findings indicate that preferential responses to the changing spectro-temporal properties of the stimuli and to the target-discrimination task involve distinct, non-overlapping areas of the secondary auditory cortex. Thus, in the present study, differences in sensory activation were not masked by the effects of attention.

Acoustic Stimulation↗
PubMed1999

Comparison of the ability of dopamine receptor agonists to inhibit forskolin-stimulated adenosine 3'5'-cyclic monophosphate (cAMP) accumulation via D2L (long isoform) and D3 receptors expressed in Chinese hamster ovary (CHO) cells.

The pharmacological properties of the human D2L (long isoform) and rat D3 dopamine receptors in functional assays were examined. A range of dopamine agonists were assessed for their ability to inhibit adenosine 3'5'-cyclic monophosphate (cAMP) accumulation via the two receptors expressed stably in Chinese hamster ovary cells. Dopamine caused a significantly greater maximal inhibition (P < 0.05) of cAMP accumulation via the D2L receptor (approximately 70%) as compared to the D3 receptor (approximately 50%). The pattern of agonist effects was different at the two receptors. The absolute and relative potencies for inhibition of cAMP accumulation were different for a range of agonists acting at the two receptors. Similarly, the maximal inhibitions achieved by a range of agonists were different for the two receptors.

Animals↗
PubMed1999

"Sparse" temporal sampling in auditory fMRI.

The use of functional magnetic resonance imaging (fMRI) to explore central auditory function may be compromised by the intense bursts of stray acoustic noise produced by the scanner whenever the magnetic resonance signal is read out. We present results evaluating the use of one method to reduce the effect of the scanner noise: "sparse" temporal sampling. Using this technique, single volumes of brain images are acquired at the end of stimulus and baseline conditions. To optimize detection of the activation, images are taken near to the maxima and minima of the hemodynamic response during the experimental cycle. Thus, the effective auditory stimulus for the activation is not masked by the scanner noise. In experiment 1, the course of the hemodynamic response to auditory stimulation was mapped during continuous task performance. The mean peak of the response was at 10.5 sec after stimulus onset, with little further change until stimulus offset. In experiment 2, sparse imaging was used to acquire activation images. Despite the fewer samples with sparse imaging, this method successfully delimited broadly the same regions of activation as conventional continuous imaging. However, the mean percentage MR signal change within the region of interest was greater using sparse imaging. Auditory experiments that use continuous imaging methods may measure activation that is a result of an interaction between the stimulus and task factors (e.g., attentive effort) induced by the intense background noise. We suggest that sparse imaging is advantageous in auditory experiments as it ensures that the obtained activation depends on the stimulus alone.

Acoustic Stimulation↗
PubMed1999

Potentiating effects of hyper-osmolality and epidermal growth factor on the release of arachidonic acid in human glomerular mesangial cells.

Studies were performed to determine the interactive effects of high concentrations of glucose (HG) and epidermal growth factor (EGF) on the release of arachidonic acid (3H-AA) in human glomerular mesangial cells (MC) in culture. Since high glucose has been reported to increase the mass of diacylglycerol (DAG) in MC, the HG-induced release of 3H-AA was compared to that initiated by the phorbol ester, PMA. It was found that when media contained high levels (25 mM) of glucose, the release of 3H-AA was increased significantly by 8.4% (change from control) after 1 h of exposure and was maintained at values not significantly different from this level for the next 2 h. After 3-h exposure, there was no significant difference between 25 and 50 mM glucose, suggesting that the effects of glucose are saturating at 25 mM. After 1-h exposure, 3H-AA release was also increased by PMA; however, the increase was larger and the peak increase was delayed until after 1 h. 3H-AA release was significantly increased by epidermal growth factor (EGF) by 8.5% after 1 h and was maintained at this level after 2 and 3 h of exposure. In the presence of HG, EGF increased 3H-AA release by 24.6% after the 1st hour and by 20.4 and 19.4%, after the 2nd and 3rd hours, respectively. Mannitol (20 mM), added as an osmotic control, increased 3H-AA release by 6.2% and also significantly enhanced the effects of EGF after 3 h. The experimental values (19.0%) for the release of 3H-AA after 3-h exposure to EGF in combination with either high glucose or mannitol were significantly greater than the expected (added) values (12.1%). These results demonstrate that as a result of an elevated solution osmolality, high glucose acts synergistically with EGF to increase the release of 3H-AA in human mesangial cells.

Arachidonic Acid↗
PubMed1999

Signalling by CXC-chemokine receptors 1 and 2 expressed in CHO cells: a comparison of calcium mobilization, inhibition of adenylyl cyclase and stimulation of GTPgammaS binding induced by IL-8 and GROalpha.

The effect of interleukin-8 (IL-8) and growth-related oncogene alpha (GROalpha) on [35S]-guanosine 5'-O-(3-thiotriphosphate) ([35S]GTPgammaS) binding, forskolin-stimulated cyclic AMP accumulation and cytosolic calcium concentration were determined in recombinant CHO cells expressing HA-tagged CXC-chemokine receptors 1 and 2 (CXCR1 and CXCR2). Radioligand binding assays confirmed that the binding profiles of the recombinant receptors were similar to those of the native proteins. IL-8 displaced [125I]-IL-8 binding to CXCR1 and CXCR2 with pKi values of 8.89+/-0.05 and 9.27+/-0.03, respectively. GROalpha, a selective CXCR2 ligand, had a pKi value of 9.66+/-0.39 at CXCR2 but a pKi>8 at CXCR1. Calcium mobilization experiments were also consistent with previous reports on native receptors. Activation of both receptors resulted in stimulation of [35S]GTPgammaS binding and inhibition of adenylyl cyclase. A comparison of the functional data at CXCRI showed that a similar potency order (IL-8> >GROalpha) was obtained in all three assays. However, at CXCR2 whilst the potency orders for calcium mobilization and inhibition of adenylyl cyclase were similar (IL-8 > or = GROalpha), the order was reversed for stimulation of [35S]GTPgammaS binding (GROalpha > IL-8). All of the functional responses at both receptors were inhibited by pertussis toxin (PTX), suggesting coupling to a Gi/Go protein. However, the calcium mobilization induced by IL-8 at CXCR1 was not fully inhibited by PTX, suggesting an interaction with a G-protein of the Gq family. Our results with pertussis toxin also suggested that, in the [35S]GTPgammaS binding assay, CXCR1 displays some constitutive activity. Thus, we have characterized the binding and several functional responses at HA-tagged CXCRs 1 and 2 and have shown that their pharmacology agrees well with that of the native receptors. We also have preliminary evidence that CXCR1 displays constitutive activity in our cell line and that CXCR2 may traffic between different PTX sensitive G-proteins.

Adenylate Cyclase Toxin↗
PubMed1998

Pharmacological characterisation of melatonin mt1 receptor-mediated stimulation of [35S]-GTPgammaS binding.

The activation of G-proteins by melatonin mt1 receptors was studied by measuring [35S]-guanosine-5'-(3-thiotriphosphate) ([35S]-GTPgammaS) binding to membranes prepared from Chinese hamster ovary (CHO) cells stably expressing human mt1 receptors. Melatonin stimulated [35S]-GTPgammaS binding in a concentration-dependent manner (pEC50, 8.77+/-0.02). The optimal (212+/-4%) increase over basal levels of binding (basal = 100%) was observed following incubation of membranes (12.5 microg protein/well) for 120 min at 30 degrees with [35S]-GTPgammaS (0.1 nM), in the presence of GDP (10 microM), NaCl (100 mM), and MgCl2 (10 mM). Melatonin analogues stimulated [35S]-GTPgammaS binding with a rank order (2-iodomelatonin > melatonin = S20098 > GR196429 > 6-chloromelatonin = 6-hydroxymelatonin >> N-acetylserotonin > or = GR135531 = mt1 luzindole = 5-HT = 0), which was identical to their affinities for the high affinity state of the receptor (correlation coefficient 0.94). All agonists evoked similar maximum increases in [35S]-GTPgammaS binding. EC50 values were 14- to 63-fold lower than binding affinities. The melatonin receptor antagonist luzindole (0.1-10 microM) evoked a parallel rightward shift in the melatonin concentration-response curve, with a pKB of 7.19+/-0.13, which is similar to its affinity in radioligand binding studies for human mt1 receptors. Stimulation of [35S]-GTPgammaS binding was abolished by pretreatment of cells with pertussis toxin (18 hr, 100 ng/mL) prior to preparation of membranes. Melatonin was without effect in CHO cells which lacked the mt1 receptor. Thus, melatonin and melatonin analogues stimulate [35S]-GTPgammaS binding with a profile which is consistent with binding to mt1 receptors causing activation of Gi/Go G-proteins.

Animals↗
PubMed1998

Activation of microtubule-associated protein kinase (Erk) and p70 S6 kinase by D2 dopamine receptors.

The ability of human and rat D2(short) and D2(long) dopamine receptors to activate microtubule-associated protein (MAP) kinase (Erk1/2) and p70 S6 kinase has been investigated in recombinant cells expressing these receptors. In cells expressing the D2(short) receptor, dopamine activated both enzymes in a transient manner but with very different time courses, with activation of Erk being much quicker. Activation of both enzymes by dopamine was dose-dependent and could be prevented by a range of selective dopamine antagonists. Excellent correlations were observed between the potencies of the antagonists for blocking enzyme activation and their affinities for the D2 dopamine receptor. Activation of Erk and of p70 S6 kinase via the D2 dopamine receptors was prevented by pretreatment of the cells with pertussis toxin, indicating the involvement of G proteins of the Gi or Go family. Inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase) were found to block substantially, but not completely, activation of p70 S6 kinase by dopamine, suggesting the involvement of PI 3-kinase-dependent and -independent signalling pathways in its control by dopamine. p70 S6 kinase activation was completely blocked by rapamycin. In the case of Erk, activation was partially blocked by wortmannin or LY294002, indicating a possible link with PI 3-kinase.

Animals↗
PubMed1998

Previous breast biopsy for benign disease rarely complicates or alters interpretation on screening mammography.

OBJECTIVE: It has been suggested that breast screening leads to too many biopsies for benign disease that permanently scar the breast and confuse the interpretation of subsequent mammograms. We undertook retrospective and prospective studies to determine how often an excisional biopsy for benign breast disease complicates or alters interpretation of screening mammograms. MATERIALS AND METHODS: Retrospective review of our screening center database yielded 31,025 asymptomatic patients who had routine mammographic screening studies between 1993 and 1996. Of the 58,538 examinations of these patients, 53,510 were of patients who had no history of breast biopsy and 5028 were of patients who had a history of breast biopsy for benign disease. Recall rates were compared between the two groups. In the prospective study, radiologists reviewed the mammograms of 1997 consecutive patients presenting to the screening center, 173 of whom reported a prior breast biopsy for benign disease. The radiologist interpreting the images determined how often evidence of the biopsy site was apparent on the mammogram and how often such changes necessitated additional imaging. RESULTS: In the retrospective study, 3296 (6%) of the 53,510 studies done in patients who did not have a biopsy for benign disease and 360 (7%) of the 5028 studies done in women who had a biopsy for benign disease led to additional imaging. Eight recalls for further imaging (0.16%) among the 5028 studies in women with a prior biopsy for benign disease were related to the biopsy site. In the prospective study, 24 (14%) of the 173 women who had a biopsy for benign disease had mammographic evidence of the biopsy site. Nine (5%) of the 173 women who had previously had a biopsy for benign disease and 86 (5%) of the 1824 patients without a prior biopsy were recalled for additional imaging. No women were recalled because a previous breast biopsy for benign disease led to confusion or diagnostic concern. CONCLUSION: Changes in patients' breasts due to previous excisional biopsies for benign breast disease rarely pose a diagnostic dilemma in the interpretation of routine screening mammograms.

Biopsy↗
PubMed1997

Polarization-enhanced NMR spectroscopy of biomolecules in frozen solution.

Large dynamic nuclear polarization signal enhancements (up to a factor of 100) were obtained in the solid-state magic-angle spinning nuclear magnetic resonance (NMR) spectra of arginine and the protein T4 lysozyme in frozen glycerol-water solutions with the use of dynamic nuclear polarization. Polarization was transferred from the unpaired electrons of nitroxide free radicals to nuclear spins through microwave irradiation near the electron paramagnetic resonance frequency. This approach may be a generally applicable signal enhancement scheme for the high-resolution solid-state NMR spectroscopy of biomolecules.

Arginine↗
PubMed1997

Evidence that antipsychotic drugs are inverse agonists at D2 dopamine receptors.

1. The effects of a number of D2-like dopamine receptor antagonists have been determined on forskolin-stimulated cyclic AMP accumulation in Chinese hamster ovary (CHO) cells expressing the human D2short dopamine receptor (CHO-D2S cells). 2. Dopamine inhibited the effect of forskolin (as expected for a D2 receptor). However, all of the antagonists tested, apart from UH232 and (-)-butaclamol, were able to increase cyclic AMP accumulation above the forskolin control level. (+)-Butaclamol elicited a similar stimulation of forskolin-stimulated cyclic AMP accumulation in a CHO cell line expressing human D2long dopamine receptors whereas it exhibited no stimulating effect on forskolin-stimulated cyclic AMP accumulation in untransfected CHO-K1 cells. 3. There was a strong correlation between the EC50 values of these compounds for potentiation of cyclic AMP accumulation and their Ki values from radioligand binding experiments in CHO-D2S cells. 4. The effects of both (+)-butaclamol and dopamine in CHO-D2S cells were inhibited by pre-treatment with pertussis toxin indicating a role for Gi/Go proteins. 5. UH232 did not significantly affect forskolin-stimulated cyclic AMP accumulation but this substance was able to inhibit the effects of both dopamine and (+)-butaclamol in a concentration-dependent manner. Thus the effects of (+)-butaclamol on forskolin-stimulated cyclic AMP accumulation are mediated directly via the D2 receptor rather than by reversal of the effects of an endogenous agonist. 6. These data suggest that the D2 dopamine receptor antagonists tested here, many of which are used clinically as antipsychotic drugs, are in fact inverse agonists at human D2 dopamine receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Agonist action at D2(short) dopamine receptors determined in ligand binding and functional assays.

Mechanisms of agonist action at the G protein-coupled D2(short) dopamine receptor expressed in Chinese hamster ovary cells have been investigated. Agonist binding was assayed in the presence and absence of GTP (100 microM). Data in the absence of GTP were fitted best by a two-site model (apomorphine, dopamine, 10,11-dihydroxy-N-n-propylnorapomorphine hydrochloride, and quinpirole) or a one-site model [bromocriptine, dihydroergocristine, and (-)-3-(3-hydroxyphenyl)-N-propylpiperidine hydrochloride], whereas in the presence of GTP a one-site model was the best fit for all compounds. Agonist binding parameters were used to provide a measure of the ability of the agonist to stabilise the ternary complex of agonist/receptor/G protein. Agonist stimulation of [35S]guanosine 5'-O-(3-thiotriphosphate) ([35S]GTPgammaS) binding for a range of agonist concentrations was measured and the EC50 and maximal effects determined. The initial rates of [35S]GTPgammaS binding induced by maximally stimulating agonist concentrations were also recorded. Simultaneous inhibition of agonist-stimulated [35S]GTPgammaS binding and receptor occupancy by spiperone was determined. Agonist inhibition of forskolin-stimulated cyclic AMP accumulation was determined for a range of agonist concentrations and the EC50 and maximal inhibition recorded. The data on the maximal agonist responses showed that it was possible to detect a spectrum of agonist efficacy (partial and full agonism) in both functional assays. The data on the apparent potencies of agonists to elicit the functional responses showed that different extents of amplification of response were seen for different agonists in both assays. The maximal activity data have been compared with the stabilisation of the agonist/receptor/G protein ternary complex as measured in binding assays.

Animals↗
PubMed1997

Screening mammography: effect of national guidelines on current physician practice.

PURPOSE: To evaluate the effect of national breast cancer screening guidelines on current physician attitudes toward and practice of screening mammography. MATERIALS AND METHODS: Questionnaire responses from 278 physicians were analyzed. The questionnaire had four sections: general information on physician practice and experience, current use of breast cancer screening, perceptions of screening mammography, and physician awareness of and response to the controversy in breast cancer screening. RESULTS: In women aged 40-49 years, 144 (52%) of 278 physicians performed annual clinical breast examination and screening mammography every 2 years; 57 (21%) favored annual mammography and clinical breast examination. In women aged 50 years and older, 232 (83%) physicians screened patients annually with clinical breast examination and mammography. Two hundred seventeen (78%) physicians were aware of the recommended changes in screening guidelines; 54 (19%) were not aware of the changes. Of those aware of the changes, 56 (26%) changed to the new guidelines, 150 (69%) did not change, and six (3%) modified their practice somewhat. CONCLUSION: Physician practice as regards screening mammography is influenced by national guidelines.

Adult↗
PubMed1997

Should women with implants or a history of treatment for breast cancer be excluded from mammography screening programs?

OBJECTIVE: Our objective was to determine whether it is scientifically justified to require that women with implants or a history of treatment for breast cancer be screened in a diagnostic mammography setting and that they be excluded from mammography screening programs. MATERIALS AND METHODS: The recall rates for women with breast implants or a history of treatment for breast cancer who were screened in a dedicated mammography screening program were compared with those of other women in the screening program. The computerized records for the breast screening program of the Department of Radiology at our institution for January 1, 1990, through December 31, 1995, were reviewed. The recall rates for women who had breast implants and those for women with a history of treatment for breast cancer were compared with the recall rates for the other women who underwent screening. Each recall rate included women who were called back for additional evaluation in addition to those for whom a biopsy was recommended on the basis of the screening study. RESULTS: Of 45,134 screening examinations done during the review period, 43,454 (96%) were for women who had no history of breast cancer or of breast implants; 590 (1%) were for women who had undergone mastectomy; 991 (2%) were for women who had been treated with lumpectomy and irradiation for breast cancer; and 99 (0.2%) were for women with breast implants. Among the 43,454 examinations of women with no history of breast cancer or implants, 3081 examinations (7%) led to interpretations that produced requests for the patient to return for additional evaluation. Thirty-six women who had been treated for breast cancer by mastectomy were recalled (6%). Seventy-five women who had undergone lumpectomy and irradiation for breast cancer were recalled (8%). Five women with breast implants were recalled (5%). Statistically, these rates were not significantly different. CONCLUSION: We find no scientific reason to exclude women who have been treated for breast cancer or who have breast implants from dedicated screening programs.

Breast Implants↗
PubMed1997

The frequency and significance of adnexal lesions incidentally revealed by CT.

OBJECTIVE: This paper describes the frequency of incidental adnexal findings revealed by routine CT scanning and determines the significance of these lesions in premenopausal and postmenopausal women, particularly in those with an already known malignancy other than ovarian carcinoma. MATERIALS AND METHODS: A computerized search of all radiology reports from 1992 identified 3448 women who underwent abdominopelvic or pelvic CT scans for an indication other than ovarian carcinoma or a known or suspected pelvic mass. Patients were divided into two subgroups: premenopausal and postmenopausal. CT reports were reviewed to identify patients with incidentally discovered adnexal lesions. Imaging characteristics and lesion size were recorded. To determine the significance of the lesions, we also reviewed clinical, radiologic, and histopathologic data. Lesions were judged to be benign on the basis of 12-month clinical follow-up, additional imaging that revealed stability or resolution, or histopathology. Lesions were judged to be malignant on the basis of progression of the lesion on subsequent imaging or histopathology. Lesions were classified as undetermined in patients with a serious or life-threatening illness who consequently underwent no further evaluation of the lesion. RESULTS: An incidental adnexal lesion was revealed by CT scanning in 168 cases (5%). Seventeen of these patients were lost to follow-up. Of the remaining 151 patients, 104 (69%) had incidental adnexal lesions that represented benign disease, 45 (30%) had undetermined lesions, and two (1%) had malignant lesions. In analyzing the two subgroups of patients, we determined that 56 (81%) of 69 premenopausal patients and 48 (59%) of 82 postmenopausal patients had benign adnexal lesions. On the basis of chart review, 67 patients had a known malignancy. Of these patients, 30 (46%) had benign adnexal disease, and 31 (48%) had undetermined findings. Four (6%) were lost to follow up, and the remaining two patients (3%) who were postmenopausal had metastatic disease of the ovaries. No primary ovarian malignancies were discovered incidentally in our study population. CONCLUSION: Our results indicate that in both premenopausal and postmenopausal women a significant proportion of adnexal lesions incidentally revealed on routine CT scanning are benign, even in women with known malignancies other than ovarian carcinoma.

Adnexal Diseases↗
PubMed1997

Patients' opinion of mammography screening services: immediate results versus delayed results due to interpretation by two observers.

OBJECTIVE: The purpose of this study was to evaluate by random questionnaire mailings the preferences of women who have undergone mammography in our region regarding communication of mammography screening results. MATERIALS AND METHODS: Questionnaires were mailed to 400 randomly selected women who were more than 35 years old and who had been treated at our institution for medical or surgical reasons. Questions regarding use of mammography screening at our institution versus services at other locations were included. The questionnaire described two possible mammography services; either a double reading service that would provide delayed reports (DRDR) with the benefit of extra cancers detected, and a service that provides immediate reports given directly to the patient by an on-site radiologist. The presentation of the services was reversed in half the questionnaires to avoid bias. Patients' choices were collected, as were demographic data. The choice of one system over the other was evaluated using the one-sample lest for binomial probability. The chi-square test was used to determine if the order of questions on the survey or the site of patients' screening mammography affected responses. RESULTS: The response rate was 42% (n = 168). Of these, one response informed us of the death of a patient. Of the remaining 167 respondents, 75% (n = 126) preferred the DRDR system, 13% (n = 22) preferred the system providing immediate results (p < .0001), and the other 19 respondents did not select a preference. Of the 167 respondents, 156 answered the question regarding previous screening mammography experience. Of the 105 patients who had undergone screening mammography at our institution, 78% (n = 82) preferred the DRDR system. Of the 51 patients who had undergone mammography elsewhere or who had never undergone mammography, 75% (n = 38) preferred the DRDR system. We found that ordering of presentation of the systems in the questionnaire had no effect on responses. Likewise, whether a respondent had undergone mammography at our institution had no effect on responses (p = 1.0). CONCLUSION: A statistically significant number of women who responded to our questionnaire preferred the DRDR system of reporting screening mammographic results. Educational material about double reading that we included with each patient's questionnaire could account for these results. If the use of a second interpreter is feasible and is done for batch interpretation of screening mammograms, then education of patients about this process may increase acceptance of a delayed mammographic report.

Adult↗
PubMed1997

Imaging of fallopian tube tumors.

OBJECTIVE: The purposes of this study were to investigate the imaging findings in patients with primary fallopian tube neoplasms and to determine whether specific imaging features favor the preoperative diagnosis of fallopian tube tumors (FTT). MATERIALS AND METHODS: Computerized search of medical records from 1984 to 1994 identified 20 patients with a discharge diagnosis of primary fallopian tube carcinoma. Medical records, imaging studies, and pathology findings were reviewed. Eleven patients had available preoperative imaging. RESULTS: Seventeen of 20 patients with primary FTT had unilateral disease. Of these 17, preoperative imaging was available in nine, showing four solid adnexal masses, four complex cystic adnexal masses, and one normal adnexa. The preoperative imaging of these nine patients included six sonographic and five CT studies. Three patients with primary FTT had bilateral tumors, and preoperative imaging was available for two patients: Two sonographic studies and one CT study showed one complex cystic adnexal mass and three normal adnexa. CONCLUSION: Primary FTT commonly presents as an adnexal mass on preoperative imaging and mimics other pelvic malignancies, especially ovarian carcinoma. Making a specific preoperative diagnosis is difficult; however, because primary FTT is unlikely to be confused with a benign process, delay in diagnosis is rare.

Adult↗
PubMed1996

P2T purinoceptors: ADP receptors on platelets.

ADP acts on platelets via the P2T purinoceptor to cause aggregation, but the way in which it does so is not fully understood. Most aggregating agents act via G protein-coupled receptors to stimulate phospholipase C (PLC) and so mobilize Ca2+ via inositol trisphosphate, whereas ADP clearly causes the mobilization of Ca2+ from internal stores but is only a weak activator of PLC. ADP also inhibits adenylate cyclase and it has been suggested that this effect is mediated by a different receptor, although evidence from antagonist studies argues against this. Studies of Ca2+ influx have shown that ADP is unique in causing a rapid influx of Ca2+, and patch-clamp studies have confirmed the activation by ADP of non-selective cation channels. This would imply the existence of two ADP receptors on platelets, a receptor-operated channel responsible for the rapid Ca2+ influx and a G protein-coupled receptor possibly linked to both inhibition of adenylate cyclase and mobilization of Ca2+. In this review the structure-activity relationships for aggregation, inhibition of adenylate cyclase and increases in cytoplasmic Ca2+ are summarized, and the relationship between these effects discussed.

Adenosine Diphosphate↗