Perspectives in receptor research: proceedings of the 10th by Dario Giardin`, Alessandro Piergentili and Maria Pigini

By Dario Giardin`, Alessandro Piergentili and Maria Pigini (Eds.)

College of Camerino, Italy. lawsuits from the 10th Camerino-Noordwijkerhout Symposium, held in Camerino, Italy, September 10-14, 1995. overseas participants.

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By Dario Giardin`, Alessandro Piergentili and Maria Pigini (Eds.)

College of Camerino, Italy. lawsuits from the 10th Camerino-Noordwijkerhout Symposium, held in Camerino, Italy, September 10-14, 1995. overseas participants.

Show description

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Additional resources for Perspectives in receptor research: proceedings of the 10th Camerino-Noordwijkerhout Symposium, Camerino, Italy, 10-14 September 1996

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1B). If the model shown in Fig. M VII interfaces present in the wild type m2 and m5 mAChRs, respectively [16]. Consistent with our working hypothesis, we found that either of the two point mutations resulted in mutant receptors which, when transiently expressed in COS-7 cells, were able to bind significant amounts ofmuscarinic radioligands (shown for C4 in Fig. 1B) and to couple to G proteins [16]. These findings therefore indicated that the model shown in Fig. 1A that guided this mutagenesis study is probably correct.

Recently, we obtained essentially similar results with the m2 mAChR (Fig. 12; ref. 46). In COS-7 cells, the m2 mAChR, a prototypical Gi/o-coupled receptor, stimulates PI hydrolysis only poorly, even in the presence of overexpressed wild type Gaq (q(wt); Figs. 12, 13). However, coexpression of the m2 receptor with qi5 or qo5 (mutant Gaq-subunits in which the last five amino acids of q(wt) were replaced with the corresponding ai2 or ao sequences, respectively) led to a pronounced stimulation (4-8-fold) of PLC activity (Figs.

Consistent with our working hypothesis, we found that either of the two point mutations resulted in mutant receptors which, when transiently expressed in COS-7 cells, were able to bind significant amounts ofmuscarinic radioligands (shown for C4 in Fig. 1B) and to couple to G proteins [16]. These findings therefore indicated that the model shown in Fig. 1A that guided this mutagenesis study is probably correct. This model was based on the recently proposed "Baldwin projection" [4,5], assuming an anticlockwise connectivity of the TM helices (as viewed from the extracellular membrane surface).

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