Homologous desensitization of beta-adrenergic receptors in lymphoma cells is not altered by the inactivation of Ni (Gi), the inhibitory guanine nucleotide regulatory protein.
We had previously demonstrated that the cyc- mutant of S49 wild-type lymphoma cells both desensitizes and undergoes a sequestration-internalization of the beta-receptor in response to short-term treatment with adrenaline. The cyc- mutant of S49 wild-type lymphoma cells lacks the alpha s subunit of the stimulatory coupling protein Ns, but has fully functional Ni, the inhibitory component of the regulatory complex. This suggested that functional Ns was not required for desensitization. To examine the role of Ni in desensitization, both S49 wild-type and cyc- cells were treated with islet-activating protein under conditions that led to over 85% attenuation of Ni function in S49 wild-type cells and approx. 50% attenuation of Ni function in cyc- cells. This treatment had no effect on the adrenaline-induced desensitization of adenylate cyclase or the sequestration event measured by the apparent movement of beta-adrenergic receptors to a light-vesicle fraction. Further, the desensitization event, which occurs before the sequestration event, observable only in intact cells, was also not altered by islet-activating-protein pretreatment of S49 wild-type cells. The data suggest that a functional Ni is not required for desensitization in the S49 lymphoma cells.
D000244:Adenosine Diphosphate / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D002474:Cell-Free System / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors*; D008223:Lymphoma / Q000378:metabolism*; D009154:Mutation; D037342:Pertussis Toxin; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D011943:Receptors, Adrenergic, beta; D010566:Virulence Factors, Bordetella; D000244:Adenosine Diphosphate; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D004837:Epinephrine