title: Additive effect of ADP and CGRP in modulation of the acetylcholine receptor channel in Xenopus embryonic myocytes.
abstract: 1. We have previously shown that the activation of either protein kinase A (PKA) or protein kinase C (PKC) enhanced the responses of muscle membrane to acetylcholine (ACh) by increasing the mean open time of embryonic-type ACh channels in Xenopus cultured myocytes. In the present study, we further investigated the interaction between these two kinases in the modulation of ACh channels by using the receptor ligands, adenosine diphosphate (ADP) and calcitonin gene-related peptide (CGRP) which selectively activate PKC and PKA, respectively. 2. ADP concentration-dependently increased the mean open time of embryonic-type ACh channels and 0.3 mM ADP is sufficient to achieve the maximal potentiating effect. alpha, beta-Methylene ATP and PMA (phorbol 12-myristate 13-acetate) but not adenosine, AMP, dibutyryl cyclic GMP have similar potentiating action. 3. Suramin (0.3 mM) pretreatment abolished the potentiating effect of ADP but left that of PMA unchanged. 4. CGRP increased the mean open time of embryonic-type ACh channels in a concentration-dependent manner and 1 microM CGRP produced the maximal effect. 5. The maximal effects of both ADP (0.3 mM) and CGRP (1 microM) in the prolongation of mean open time of ACh channels were additive. 6. These results suggest that the modulation of embryonic-type ACh channels by the endogenously released ligands via the activation of PKA and PKC is additive and possibly different sites of ACh channels may be involved in the potentiation effect of either PKC or PKA.
authors.affiliation: Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
authors.forename: J C
authors.initials: JC
authors.lastname: Liou
authors.forename: W M
authors.initials: WM
authors.lastname: Fu
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000378:metabolism; D011983:Receptors, Purinergic / Q000187:drug effects / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: D011950:Receptors, Cholinergic; D011983:Receptors, Purinergic; D003995:Dibutyryl Cyclic GMP; D013498:Suramin; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D015740:Calcitonin Gene-Related Peptide; D013755:Tetradecanoylphorbol Acetate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate