A study of the local modulatory effect of nitric oxide and histamine on neurotransmission in the mouse vas deferens

The effects of Nitric Oxide (NO) and histamine as modulatory agents of autonomic neurotransmission in the mouse vas deferens have been investigated. Electrophysical, pharmacological, and histochemical approaches were adopted to investigate their various activities.;Mechanical responses evoked by electrical field stimulation gave information about pre- and post-junctional effects. Whereas agonist evoked contractions gave information about post-junctional responses, L-arginine (3x10-6M) reduced nerve evoked contractions, suggesting a NO sensitivity. L-arginine methyl ester (L-AME) 2.3x10-4M (NOsynthase inhibitor), increased nerve evoked contractions. This suggested a physiological depressive role for NOsynthase. L-arginine shifted the dose-response curve to the right, whereas L-AME shifted the curve to the left, indicating a post-junctional modulatory mode of action. Extracellular focal recording techniques recorded excitatory junction currents (EJCs). EJCs reflect the neuronal release of ATP. Quantal analysis of EJCs amplitude permitted the determination of pre- and post-junctional effects. L-arginine (3.4x10-4M) reduced EJCs amplitude and mean quantal content. Quantal analysis also revealed a pre-junctional mode of action. PTI0 (3x10-8M) increased EJCs amplitude, and reversed the inhibitory effect of L-arginine. L-arginine revealed a low threshold current of a positive polarity, abolished by noradrenaline and increased by yohimbine and idazoxan, indicating a possible existence of autoinhibitory feedback mechanisms controlling the new current.;Exogenous histamine reduced EJCs amplitude. Quantal analysis revealed both pre- and post-junctional sites of action. Thioperamide (10-7M) and (R)--methyl histamine (10-8M) confirmed the presence of H3-receptors pre-junctionally. Ranitidine (10-5M) and dimaprite (10-6M) confirmed the presence of H2-receptors pre- and post-junctionally. The presence of H2 and H3 receptors indicate that endogenous histamine acts on those receptors to depress contraction.;The results showed that NO-mediated neuromodulatory mechanisms exist in this tissue, which modulate pre- and post-junctional activities. The results confirmed the presence of pre-junctional H3- receptors, and pre- and post-junctional H2 receptors. Both receptors modulate transmission in this tissue.