Hypertonicity-induced transmitter release at Drosophila neuromuscular junctions is partly mediated by integrins and cAMP/protein kinase A

J Physiol. 2002 Jan 1;538(Pt 1):103-19. doi: 10.1113/jphysiol.2001.012901.


The frequency of quantal transmitter release increases upon application of hypertonic solutions. This effect bypasses the Ca(2+) triggering step, but requires the presence of key molecules involved in vesicle fusion, and hence could be a useful tool for dissecting the molecular process of vesicle fusion. We have examined the hypertonicity response at neuromuscular junctions of Drosophila embryos in Ca(2+)-free saline. Relative to wild-type, the response induced by puff application of hypertonic solution was enhanced in a mutant, dunce, in which the cAMP level is elevated, or in wild-type embryos treated with forskolin, an activator of adenylyl cyclase, while protein kinase A (PKA) inhibitors decreased it. The response was also smaller in a mutant, DC0, which lacks the major subunit of PKA. Thus the cAMP/PKA cascade is involved in the hypertonicity response. Peptides containing the sequence Arg-Gly-Asp (RGD), which inhibit binding of integrins to natural ligands, reduced the response, whereas a peptide containing the non-binding sequence Arg-Gly-Glu (RGE) did not. A reduced response persisted in a mutant, myospheroid, which expresses no integrins, and the response in DC0 was unaffected by RGD peptides. These data indicate that there are at lease two components in the hypertonicity response: one that is integrin mediated and involves the cAMP/PKA cascade, and another that is not integrin mediated and does not involve the cAMP/PKA cascade.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Animals
  • Calcium / pharmacology
  • Colforsin / pharmacology
  • Cyclic AMP / physiology*
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / physiology*
  • Drosophila / embryology
  • Drosophila / genetics
  • Drug Synergism
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Hypertonic Solutions / pharmacology*
  • Integrins / physiology*
  • Mutation / physiology
  • Neuromuscular Junction / metabolism*
  • Neurotransmitter Agents / metabolism*
  • Oligopeptides / pharmacology
  • Reference Values
  • Synaptic Transmission / drug effects


  • Enzyme Inhibitors
  • Hypertonic Solutions
  • Integrins
  • Neurotransmitter Agents
  • Oligopeptides
  • Colforsin
  • glycyl-arginyl-glycyl-aspartyl-seryl-proline
  • glycyl-arginyl-glycyl-aspartyl-serine
  • glycyl-arginyl-glycyl-glutamyl-seryl-proline
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Adenylyl Cyclases
  • Calcium