We have previously reported that phosphorylation of adenylyl cyclase type VI (AC6) may result in the suppression of adenylyl cyclase activity during desensitization of the A2a-adenosine receptor-mediated cAMP response (A2a desensitization) in rat pheochromocytoma PC12 cells. In the present study, we demonstrate that protein kinase C (PKC) is responsible for the phosphorylation and inhibition of...

Conditions have been developed for desensitizing the beta-adrenergic receptor-coupled adenylate cyclase of turkey erythrocytes in a cell-free system. Desensitization is observed when cell lysates are incubated with isoproterenol or cAMP analogs for 30 min at 37 degrees C. Maximally effective concentrations of isoproterenol produce a 41.0 +/- 1.55% loss of iosproterenol-stimulated and a 15.0 +/-...

Organ donors are sometimes found "unsuitable" due to the presence of donor-specific anti-HLA antibodies in the recipient. In recent years, improved desensitization protocols have successfully helped to overcome HLA incompatibility hurdle. We present three cases where optimum desensitization was achieved in patients with the donor-specific anti-HLA antibody (DSA) leading to successful renal tran...

thereby representing a novel time course for desensitization. Our starting dose was higher than the 0.02-mg starting dose administered to a non-HIV patient during fluconazole desensitization; however, our initial dose was equal to or less than other protocols involving HIV-infected patients.1,5,6 Given this patient’s HIV status, we used a cautious desensitization approach (eg, dose escalation e...

OBJECTIVES We hypothesized that a standardized outpatient clopidogrel desensitization protocol would be safe and effective. BACKGROUND Adverse reactions to clopidogrel are not uncommon, and affected patients must switch to ticlopidine after drug-eluting stent placement, despite its more malignant side-effect profile, because of the risk of ischemic events associated with premature discontinua...

Signaling mechanisms coupled to activation of different neurotransmitter receptors interact in the enteric nervous system. ACh excites myenteric neurons by activating nicotinic ACh receptors (nAChRs) and muscarinic receptors expressed by the same neurons. These studies tested the hypothesis that muscarinic receptor activation alters the functional properties of nAChRs in guinea pig small intest...

In studying chimeras of NR2A and NR2C subunits of the NMDA receptor, we have found that glycine-independent desensitization depends on two regions of the extracellular N-terminal domain. One corresponds to a stretch of approximately 190 amino acids preceding the glutamate-binding domain S1. The other localizes at the interface between the N-terminal segment and the first transmembrane domain of...

A fast perfusion system was used to apply excitatory amino acids to embryonic hippocampal neurons grown in dissociated culture and voltage clamped in the whole-cell recording configuration. Responses to quisqualic acid and DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA; a potent quisqualate-like agonist) showed rapid desensitization: at 100 microM the peak inward current dec...

Spontaneous beating of heart-cell aggregates from 4-day chick embryos was initially blocked by 10(-5) g/ml tetrodotoxin (TTX). With continued exposure to the drug, the fraction of blocked aggregates decreased from about 80% at 15 min to about 25% at 2-3 h, at which time, beating aggregates had become desensitized to the toxin, showing no response to a fresh dose. Aggregates from 5-day hearts we...

BACKGROUND Kidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response...