In vitro pharmacology of inosine, with special reference to possible interactions with capsaicin-sensitive mechanisms and inflammatory mediators.

The in vitro pharmacology of inosine (Ino), a putative anti-inflammatory compound, has been investigated in smooth muscle preparations, with emphasis on its possible interaction with known inflammatory mediators, as well as capsaicin, an inducer of "neurogenic inflammation". The highest concentration of Ino routinely studied was 1 mM, since 10 mM nonspecifically inhibited many types of smooth muscle motor responses. In the guinea pig isolated ileum or trachea, Ino (1 mM) failed to influence the excitatory effect of capsaicin.

The NANC relaxation of the human ileal longitudinal and circular muscles is inhibited by MRS 2179, a P2 purinoceptor antagonist.

Aims: Functional innervation of the human small intestine may be different from that of experimental animals. These experiments set out to assess the mediating roles of P(2) purinoceptors in the non-adrenergic, non-cholinergic (NANC) relaxation of the human ileum longitudinal and circular muscles.

Main Methods: In organ bath experiments NANC relaxations were evoked by electrical field stimulation (EFS).

Role of extrinsic afferent neurons in gastrointestinal motility.

Capsaicin-sensitive extrinsic afferent nerves have been demonstrated to release biologically active substances in the gastrointestinal (GI) tract. This fact may be useful for identifying sensory transmitter substances in isolated organ experiments. In the GI tract of animals neuropeptides like tachykinins and calcitonin gene-related peptide (CGRP) mediate specific excitatory and inhibitory effects of capsaicin; some evidence indicates a participation of purinergic mechanisms as well.

P2 purinoceptor antagonists inhibit the non-adrenergic, non-cholinergic relaxation of the human colon in vitro.

Neurotransmitters released by myenteric neurons regulate movements of intestinal smooth muscles. There has been little pharmacological evidence for a role of purinergic mechanisms in the non-adrenergic, non-cholinergic (NANC) relaxation of the human large intestine. We used P(2) purinoceptor antagonists to assess whether such receptors are involved in the NANC relaxation of the circular muscle of the human sigmoid colon.

Purinergic nerves mediate the non-nitrergic relaxation of the human ileum in response to electrical field stimulation.

There has been no direct functional evidence for a purinergic innervation of the human intestinal muscle. In the present study, the relaxant effects of electrical field stimulation (1 or 10 Hz for 20s), ATP, and isoprenaline were studied in organ bath experiments on precontracted circular muscle strips of the human ileum. Non-adrenergic, non-cholinergic relaxations in response to electrical field stimulation in the presence of a nitric oxide synthase inhibitor were significantly reduced by the P(2) purinoceptor antagonists pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 50 microM) or suramin (100 microM).