Modulatory role of adenylyl cyclase and protein kinase A (PKA) in 5-hydroxytriptamines₃ induced intracellular calcium increase in parasympathetic neurons of rat major pelvic ganglia

Purpose: Serotonin has effects on the bladder contraction or urethral sphincter tone. Different subtypes of 5-hydroxytriptamine (5-HT) receptors appear to mediate the effects of serotonin on voiding. 5-HT₁ and 5-HT₂, metamorphic receptors, are examined well. However 5-HT₃, ionotrophic receptors, are not examined well. Pelvic ganglia provide the majority of the innervation of the lower urinary tract. Major pelvic ganglia (MPG) in rats are autonomic ganglia, containing both sympathetic and parasympathetic neurons related with voiding. We examined the modulatory role of adenylyl cyclase (AC) and protein kinase A (PKA) in 5-HT₃ induced intra cellular calcium increase in rat MPG. Materials and methods: The regulatory effects by AC and PKA were investigated in a single neuron of male rat major pelvic ganglia using patch clamp and fluorescence Ca²⁺ measurement techniques. Results: Inward currents were induced by 5-HT (10 μM) at only parasympathetic neurons of MPG. MDL7222 (10^-6 M), selective 5-HT₃ receptor antagonists, completely abolished the 5-HT induced inward currents. 5-HT (10 μM) induced intracelluar increases of calcium. These increases were blocked by an AC inhibitor SQ22536 (2×10^-5 M) and myristoylated PKA inhibitor (10^-7 M). Furthermore, foskolin (10^-6M), AC activator, augmented the 5-HT induced intracellular calcium increase. Conclusions: The activation of AC/PKA-dependent pathway could enhance 5-HT₃ induced intacellular calcium increase in parasympathetic neurons of rat MPG and these is helpful for the better understanding the mechanisms of the bladder contraction or urethral sphincter tone.