To investigate regulatory domains of the thromboxane A2 (TxA2) receptor, we constructed a truncated form of the mouse TxA2 receptor and expressed it in a mesangial cell line. The mutant receptor lacked 22 amino acids in the C-terminus including four potential phosphorylation sites. Ligand binding of mutant receptors was identical with the wild type. Stimulation with TxA2 agonist induced increas...

The goal of the present study was to assess the catecholamine secretory capabilities of rainbow trout Oncorhynchus mykiss chromaffin cells experiencing desensitization of the nicotinic receptor. It was hypothesized that the potential to secrete catecholamines could be maintained under conditions of nicotinic receptor desensitization owing to activation of non-cholinergic release pathways. An in...

Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate.This study was a prospectiv...

OBJECTIVES The incidence of hypersensitivity reactions (HR) is increased in patients treated with multiple courses of carboplatin. The purposes of this investigation were to evaluate the effectiveness of a 12-step desensitization protocol and to characterize the immune mechanism of carboplatin HR. METHODS We analyzed 10 consecutive patients who had documented HR to carboplatin and in whom con...

Acute desensitization is a common property of G(i/o)-coupled receptors. Recent data, however, suggest that, unlike μ-opioid receptors (MORs) located somatodendritically in neurons or expressed in heterologous systems, MORs in the presynaptic compartment of neurons are resistant to acute desensitization. It is not yet clear whether this differential desensitization is a shared property of many G...

We report on the successful desensitization of an adult female with Pompe disease who had previously experienced anaphylaxis to intravenous alglucosidase alfa therapy. The starting alglucosidase alfa dose for desensitization was 10mg/kg with gradual dose escalation and desensitization via serial dilution was completed over five infusions. This methodology serves as a means to desensitize patien...

Background Rapid drug desensitization (RDD) is widely used to re-introduce medications that have caused an IgEmediated hypersensitivity in allergic patients. However, RDD protocols are largely based on empiric experience and few in vitro models have explored the rationale guiding the rate at which the dose should be increased, what the starting dose should be and how the time elapsed between do...

The biochemical mechanisms of adenylate cyclase desensitization in arginine vasopressin-responsive epithelial cells remain unclear. Preincubation of cultured rabbit renal cortical collecting tubular cells with arginine vasopressin leads to a 30-100% decline in arginine vasopressin-stimulated adenylate cyclase activity. This loss of adenylate cyclase activity is time- and arginine vasopressin co...

Potential G protein-coupled receptor kinase (GRK) and protein kinase A (PKA) mediation of homologous desensitization of corticotropin-releasing factor type 1 (CRF1) receptors was investigated in human retinoblastoma Y-79 cells. Inhibition of PKA activity by PKI(5-22) or H-89 failed to attenuate homologous desensitization of CRF1 receptors, and direct activation of PKA by forskolin or dibutyryl ...

AMPA- and kainate (KA)-selective ionotropic glutamate receptors (iGluRs) respond to agonist by opening (gating), then closing (desensitizing) in quick succession. Gating has been linked to agonist-induced changes within the ligand-binding domain (LBD), and desensitization to rearrangement of a dimer formed by neighboring LBDs. To explore the role of dimer conformation in both gating and desensi...