Signal transduction mechanisms operated via receptor activation in the smooth muscle

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The present study was to investigate the effects of carbachol and histamine on membrane currents in single smooth muscle cells of guinea-pig ileum using a patch-clamp technique and on tension in beta -escin-skinned smooth muscle of the same intesitine, in an attempt to elucidate signal transduction systems involved in both activation of cationic channels and release of Ca^<2+> stores brought about by stimulation of eigher muscarinic or histamine receptors.1. Both cationic current and Ca^<2+>-store release elicited by histamine are indistinguishable in pharmacological properties from those elicited by carbachol.2. A G-protein system plays a role in each of the two cellular responses to either receptor stimulation, but a G-protein involved in the release of Ca^<2+> stores is characterized by insensitivity to pertussis toxin.3. Both receptor agonists act on caffeine-sensitive stores to release Ca^<2+> via formation of inositol trisphosphate (IP3).4. The cationic current in response to receptor stimulation is potentiated by a rise in cytosolic Ca^<2+> due to release of Ca^<2+> stores. Generation of oscillations in the cationic current may involve cyclical release of Ca^<2+> stores which is triggerd by IP3 formed during receptor stimulation.