Inositol Lipid Breakdown in Receptor-Mediated Responses of Sympathetic Ganglia and Sympathetically Innervated Tissues

Summary

Some peripheral tissues, including hepatocytes and aortic smooth muscle, possess vasopressin-responsive receptors of the V₁-type. Activation of these receptors causes phosphodiesterase-catalyzed breakdown of phosphatidylinositol 4,5-bisphosppate (Ptdlns4,5P₂) and leads to a rise in cytosol [$C{a^{{2^ + }}}$]. It has previously been assumed that these V₁-receptors are mainly responsive to changes in the concentration of circulating argininevasopressin (AVP). However, we have now identified a vasopressin-like neuropeptide (VLP) in the major noradrenergic neurones of sympathetic ganglia and in nerve fibers within sympathetically innervated tissues. It seems possible that VLP will prove to be a co-transmitter that is released with noradrenaline at sympathetic nerve terminals and varicosities, in which case VLP, rather than AVP, may be the predominant activator of V₁-receptors in vivo. In addition, AVP produces a striking stimulation of Ptdlns4,5P₂ breakdown in isolated superior cervical sympathetic ganglia: this response is mediated by V₁-receptors and it persists when ganglia are stimulated in a medium of low Ca²⁺ concentration or in the presence of indomethacin. A smaller stimulation of inositollipid breakdown occurs in ganglia depolarized by high [K⁺) (in the presence of 10 uM atropine): this response requires extracellular Ca²⁺ and is insensitive to V₁-receptor blockade.