Introduction of the 5-HT3B subunit alters the functional properties of 5-HT3 receptors native to neuroblastoma cells.

The identification of a second 5-HT(3) (5-HT(3B)) subunit provides an explanation for 5-HT(3) receptor heterogeneity. We investigated whether introduction of recombinant 5-HT(3B) subunits would alter the functional properties of mouse neuroblastoma 5-HT(3) receptors. RT-PCR analysis revealed that NB41A3 cells contain mRNAs encoding 5-HT(3A) and 5-HT(3B) subunits. 5-HT increased intracellular Ca(2+) concentration ([Ca(2+)](i)) and caused the concentration-dependent activation of inward currents recorded at -60 mV. Both actions of 5-HT were antagonized by ondansetron. The 5-HT concentration-response relationship of NB41A3 cells was indistinguishable from that of the related NG108-15 cell line. The selective 5-HT(3)-receptor agonist mCPBG also elevated [Ca(2+)](i) and activated inward currents. 2-M-5HT was less efficacious than 5-HT as an activator of 5-HT(3) receptors in NB41A3 cells and did not significantly increase [Ca(2+)](i). The 5-HT induced increase in [Ca(2+)](i) did not involve caffeine- or thapsigargin-sensitive intracellular Ca(2+) stores. The introduction of the 5-HT(3B) subunit by transient transfection of NB41A3 cells caused 5-HT to become less potent as an activator of 5-HT(3) receptors and altered the kinetics of 5-HT activated currents so that they resembled currents mediated by 5-HT(3AB) receptors. The 5-HT(3B) subunit also abolished the 5-HT induced [Ca(2+)](i) increase seen in untransfected NB41A3 cells. These data are consistent with the hypothesis that NB41A3 cells predominantly express homomeric 5-HT(3A) receptors that become heteromeric 5-HT(3AB) receptors upon introduction of the recombinant 5-HT(3B) subunit.

Functional properties of Cav1.3 (alpha1D) L-type Ca2+ channel splice variants expressed by rat brain and neuroendocrine GH3 cells.

Ca(2+) enters pituitary and pancreatic neuroendocrine cells through dihydropyridine-sensitive channels triggering hormone release. Inhibitory metabotropic receptors reduce Ca(2+) entry through activation of pertussis toxin-sensitive G proteins leading to activation of K(+) channels and voltage-sensitive inhibition of L-type channel activity. Despite the cloning and functional expression of several Ca(2+) channels, those involved in regulating hormone release remain unknown. Using reverse transcription-polymerase chain reaction we identified mRNAs encoding three alpha(1) (alpha(1A), alpha(1C), and alpha(1D)), four beta, and one alpha(2)-delta subunit in rat pituitary GH(3) cells; alpha(1B) and alpha(1S) transcripts were absent. GH(3) cells express multiple alternatively spliced alpha(1D) mRNAs. Many of the alpha(1D) transcript variants encode "short" alpha(1D) (alpha(1D-S)) subunits, which have a QXXER amino acid sequence at their C termini, a motif found in all other alpha(1) subunits that couple to opioid receptors. The other splice variants identified terminate with a longer C terminus that lacks the QXXER motif (alpha(1D-L)). We cloned and expressed the predominant alpha(1D-S) transcript variants in rat brain and GH(3) cells and their alpha(lD-L) counterpart in GH(3) cells. Unlike alpha(1A) channels, alpha(1D) channels exhibited current-voltage relationships similar to those of native GH(3) cell Ca(2+) channels, but lacked voltage-dependent G protein coupling. Our data demonstrate that alternatively spliced alpha(1D) transcripts form functional Ca(2+) channels that exhibit voltage-dependent, G protein-independent facilitation. Furthermore, the QXXER motif, located on the C terminus of alpha(1D-S) subunit, is not sufficient to confer sensitivity to inhibitory G proteins.

[Abnormality of hepatic perfusion in superior vena caval obstruction syndrome. A case report diagnosed by CT scan]. / Trouble de la perfusion hépatique au cours d'un syndrome cave supérieur. A propos d'un cas exploré en tomodensitométrie.

We describe a case of focal and intense contrast enhancement on hepatic CT due to superior vena caval obstruction and brachiocephalic vein obstruction. This phenomenon is explained by systemic portal venous shunting.

A comparison of pulse oximetry and respiratory rate in patient screening.

OBJECTIVE: To examine how well respiratory rate correlates with arterial oxygen saturation status as measured by pulse oximetry, and determine whether respiratory rate measurements detect oxygen desaturation reliably. METHODS: Respiratory rate (RR) and oxygen saturation (SaO2) were measured prospectively on 12,096 consecutive adult emergency department triage patients at a university medical center. Respiratory rate was measured by counting ausculated breath sounds for 1 min. Pulse oximetry was used to measure SaO2. Measurements were analysed by age (with one group for 18-19 year olds, groups for every 10 yr from age 20 to age 60, and groups for every 5 yr for subsequent ages). Pearson correlation coefficients were calculated for each age group as well as the weighted average coefficient. Cases having oxygen saturation below 90% were examined to determine how frequently they exhibited increased RR (increased RRs were defined as any rate in the upper five percentile by age. RESULTS: Correlation coefficients ranged from 0.379 to -0.465 with a weighted mean of -0.160. Coefficients for ages 18 through 70 years (representing 10,740 patients) all had magnitude < 0.252. Overall, only 33% of subjects with oxygen saturation below 90% exhibited increased RR. CONCLUSIONS: Respiratory rate measurements correlate poorly with oxygen saturation measurements and do not screen reliably for desaturation. Patients with low SaO2 do not usually exhibit increased RR. Similarly, increased RR is unlikely to reflect desaturation.

Effect of routine emergency department triage pulse oximetry screening on medical management.

PURPOSE: To determine the utility of routine triage pulse oximetry screening in emergency department (ED) patients. DESIGN: Prospective study using pulse oximetry to measure oxygen saturation of ED patients at triage. Saturation values were disclosed to physicians only after they completed medical evaluations and were ready to discharge or admit each patient. We measured changes in medical management initiated after disclosure of pulse oximetry values. SETTING AND PARTICIPANTS: The study included 14,059 consecutive patients presenting to triage at a university ED. MEASUREMENTS: Changes in select diagnostic tests: chest radiography, CBC count, spirometry, arterial blood gases, pulse oximetry, and ventilation-perfusion scans; treatments: antibiotics, beta-agonists, supplemental oxygen; and hospital admission and final diagnoses that occurred after disclosure of triage pulse oximetry values. RESULTS: Of 1,175 patients having triage pulse oximetry values less than 95%, physicians ordered repeat pulse oximetry on 159 (13.5%), additional chest radiography on 5.4%, CBC count on 3.1%, arterial blood gases on 2.9%, spirometry on 0.9%, and ventilation-perfusion scans on 0.3%. Physicians ordered 178 new therapies on 134 patients (11.4%), including supplemental oxygen for 6.5%, antibiotics for 3.9%, and beta-agonists for 1.8%. Thirty-five patients (3.0%) initially scheduled for hospital discharge were subsequently admitted. Physicians changed or added diagnoses in 77 patients (6.6%). CONCLUSIONS: Providing physicians with routine triage pulse oximetry measurements resulted in significant changes in medical treatment of these patients.