title: Effects of amylin and other peptide hormones on Na+-K+ transport and contractility in rat skeletal muscle.
abstract: 1. In skeletal muscle, catecholamines and calcitonin gene-related peptide (CGRP) increase the content of cAMP, which mediates stimulation of the Na+-K+ pump. Amylin is structurally very similar to CGRP and also increases cAMP in muscle. 2. In isolated rat soleus and extensor digitorum longus muscle, amylin produced a rapid and marked decrease in intracellular Na+, which was maintained for several hours. In soleus, amylin was found to induce a 45 % stimulation of Na+ efflux, a 43 % increase in 86Rb influx and a rise in intracellular K+. All these effects were abolished by ouabain, indicating that amylin produces acute stimulation of the Na+-K+ pump. 3. In contrast, neither the closely related peptides islet amyloid polypeptide (IAPP) and adrenomedullin nor other peptide hormones (C peptide, neuropeptide Y or substance P) produced any detectable change in intracellular Na+ or K+ uptake in soleus. 4. When contractility in soleus was inhibited by increasing extracellular K+ to 12.5 mM, amylin (10-8 M) and insulin (0.7 x 10-8 M) both induced partial recovery of force. These effects were additive, and in combination the two hormones elicited 63 and 80 % recovery of tetanic and twitch force, respectively. Higher concentrations produced even larger increases, and all effects were blocked by ouabain. 5. In buffer containing 12.5 mM K+, dibutyryl cAMP induced 71 % force recovery, which was increased by theophylline. The results indicate that amylin (like catecholamines, cAMP, CGRP and insulin) stimulates the Na+-K+ pump and thereby improves the contractility of depolarized skeletal muscle cells. This adds further support to the concept that the Na+-K+ pump is important for the maintenance of excitability in skeletal muscle.
authors.affiliation: Department of Physiology, University of Aarhus, DK-8000 Arhus C, Denmark. tc@fi.au.dk
authors.forename: T
authors.initials: T
authors.lastname: Clausen
mesh_terms: D053607:Adrenomedullin; D000682:Amyloid / Q000502:physiology*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002096:C-Peptide / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D058228:Islet Amyloid Polypeptide; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
chemical_list: D000682:Amyloid; D002096:C-Peptide; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D009479:Neuropeptides; D010455:Peptides; D053607:Adrenomedullin; D013373:Substance P; D010042:Ouabain; D012964:Sodium; D013806:Theophylline; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium