Tension of the skeletal muscle is solely controlled by excitatory cholinergic motor neurons. By contrast, the peripheral smooth muscle tissues are dual-controlled by nonadrenergic noncholinergic (NANC) inhibitory neurons as well as excitatory neurons. In the gastrointestinal tract, many possible candidates, including peptides, amino acids, nucleotides and gaseous compounds, for the inhibitory mediator and mechanisms of their inhibitory control have been extensively studied. This article introduces the diversity of inhibitory mediators and their probable intracellular mechanisms on the basis of recent findings on this theme, many of which are unexpected interesting findings.

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We investigated the relationship between tension development and the cytosolic free Ca²⁺ level ([Ca²⁺]₁) in responses to norepinephrine (NE) and selective α₂-adrenoceptor agonist, UK14, 304 of the endothelium-denuded rat aorta loaded with fura PE-3. NE (3×10^-8 M) evoked a rapid increase in [Ca²⁺]₁ followed by slight decreasing to a steady state level and produced a contraction. After the NE-induced increase in [Ca²⁺]₁ had reached a maximum, the [Ca²⁺]₁ showed persistent oscillations. The Ca²⁺ oscillations were super-imposed on the sustained increase in [Ca²⁺]₁ . UK14, 304 (3×10^-6 M) also evoked an increase in [Ca²⁺]₁ and produced a contraction. However, the UK14, 304-induced effect on [Ca²⁺]₁ was characterized by pronounced oscillations, and the amplitude of the sustained increase in [Ca²⁺]₁ was less than that seen with NE. Protein kinase C inhibitor, Ro31-8220 (3×10^-6 M) and verapamil (10^-5 M) abolished both NE- and UK14, 304-evoked Ca²⁺ oscillations. UK14, 304-induced contractions were also strongly inhibited by Ro31-8220 and verapamil. However, NE-induced contractions were partly inhibited by these inhibitors. The sustained increases in [Ca²⁺]₁ evoked NE and UK14, 304 were not significantly inhibited by Ro31-8220 and verapamil. These results suggest that NE and UK14, 304 produce Ca²⁺ oscillations during sustained contractions in rat aorta. The α₂-adrenoceptor agonist, UK14, 304-induced sustained contraction and Ca²⁺ oscillations may be due to PKC activation and opening of voltage-dependent L-type Ca²⁺ channels.

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