title: Neuronal-type acetylcholine receptors and regulation of alpha 7 gene expression in vertebrate skeletal muscle.
abstract: Several neuronal nicotinic acetylcholine receptor (AChR) genes are expressed in chick skeletal muscle during development. One of the most abundantly expressed is alpha 7, which produces a protein capable of binding alpha-bungarotoxin and is physically distinct from muscle AChRs containing the alpha 1 gene product. We show here that the alpha 7-containing species in muscle is indistinguishable pharmacologically from alpha 7-containing AChRs in neurons. In addition, immunologic analysis with subunit-specific muscle antibodies shows that the alpha 7-containing species in muscle lacks the beta 1 and delta muscle AChR gene products as it does the alpha 1. RNase protection experiments measuring alpha 7 mRNA levels indicate that the alpha 1 and alpha 7 genes may, in part, be subject to similar kinds of regulation in the tissue. Surgical denervation of leg muscle in newly hatched chicks caused a small and transient increase in alpha 7 mRNA after 8 days, while alpha 1 transcripts underwent a large and sustained increase in number. Similarly, treating myotube cultures with tetrodotoxin caused a modest increase in alpha 7 transcript levels and a large increase in alpha 1. Calcitonin gene-related peptide (CGRP) increased both kinds of transcripts in myotube cultures equally as did treatment with 8-bromo-cyclic AMP; CGRP is thought to work via a cyclic AMP-dependent pathway in muscle. In at least one respect, however, alpha 7 expression in muscle differs qualitatively from that of alpha 1: AChR-inducing activity (ARIA) increased alpha 1 mRNA levels in culture while slightly depressing alpha 7 mRNA levels. The regulatory pattern of alpha 7 expression in muscle may combine features of both alpha 7 expression in neurons and alpha 1 expression in muscle.
authors.affiliation: Department of Biology, University of California, San Diego, La Jolla 92093-0357, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Romano
authors.forename: P C
authors.initials: PC
authors.lastname: Pugh
authors.forename: J M
authors.initials: JM
authors.lastname: McIntosh
authors.forename: D K
authors.initials: DK
authors.lastname: Berg
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D002038:Bungarotoxins / Q000378:metabolism / Q000494:pharmacology; D019556:COS Cells / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002478:Cells, Cultured / Q000737:chemistry; D002642:Chick Embryo; D002645:Chickens; D018679:Cholinergic Agonists / Q000378:metabolism / Q000494:pharmacology; D004558:Electric Stimulation; D005786:Gene Expression Regulation / Q000502:physiology; D015151:Immunoblotting; D007457:Iodine Radioisotopes; D009046:Motor Neurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000196:embryology / Q000294:innervation; D012333:RNA, Messenger / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D013779:Tetrodotoxin / Q000494:pharmacology; D014714:Vertebrates
chemical_list: D000911:Antibodies, Monoclonal; D002038:Bungarotoxins; D018679:Cholinergic Agonists; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013779:Tetrodotoxin; D015740:Calcitonin Gene-Related Peptide