Tyrosine kinase involvement in apamin-sensitive inhibitory responses of rat distal colon

• Published in: The Journal of physiology Vol. 514; no. 1; pp. 177 - 188
• Main Authors: Takeuchi, Tadayoshi, Kishi, Masami, Hirayama, Nobue, Yamaji, Michiru, Ishii, Toshiaki, Nishio, Hideaki, Hata, Fumiaki, Takewaki, Tadashi
• Format: Journal Article
• Language: English
• Published: Oxford, UK The Physiological Society 01.01.1999; Blackwell Science Ltd; Blackwell Science Inc
• Subjects: 8-Bromo Cyclic Adenosine Monophosphate - analogs & derivatives; 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Animals; Apamin - pharmacology; Calcium - metabolism; Charybdotoxin - pharmacology; Colon - chemistry; Colon - drug effects; Colon - enzymology; Cyclic AMP - metabolism; Electric Stimulation; Enzyme Inhibitors - pharmacology; Genistein - pharmacology; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle, Smooth - chemistry; Muscle, Smooth - drug effects; Muscle, Smooth - enzymology; Neuropeptides - pharmacology; Neurotransmitter Agents - pharmacology; Phenols - pharmacology; Pituitary Adenylate Cyclase-Activating Polypeptide; Potassium Channel Blockers; Potassium Channels - physiology; Protein-Tyrosine Kinases - metabolism; Rats; Rats, Wistar; Research Papers; Thionucleotides - pharmacology; Tyrphostins - pharmacology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1111/j.1469-7793.1999.177af.x

It has been suggested that pituitary adenylate cyclase activating peptide (PACAP) may be involved in the non-adrenergic, non-cholinergic (NANC) inhibitory response of longitudinal muscle of rat distal colon. In this study, we have investigated the intracellular mechanism of PACAP-induced relaxation in this muscle. PACAP induced an apamin-sensitive relaxation of the longitudinal muscle. The tyrosine kinase inhibitors genistein at 10 μ m and tyrphostin 25 at 30 μ m , but not the cyclic AMP-dependent protein kinase inhibitor R p -8-bromoadenosine-3′,5′-cyclic monophosphorothioate at 30 μ m significantly inhibited the PACAP-induced relaxation to 60% and 25% of control values, respectively. PACAP did not increase the cyclic AMP content of the muscle. Tyrphostin 25 at 10 μ m significantly inhibited the relaxation of longitudinal muscle induced by electrical field stimulation (EFS), to 50% of control values. Apamin at 1 μ m , an antagonist of small conductance Ca 2+ -activated K + channels, also inhibited the relaxation, to 42% of control values. The inhibitory effects of tyrphostin 25 and apamin were not additive (44% of control values). PACAP induced an apamin-sensitive, slow hyperpolarization of the cell membrane of the muscle. Tyrphostin 25 at 3 μ m inhibited this PACAP-induced hyperpolarization. Tyrphostin 25 at 10 μ m and genistein at 10 μ m inhibited the apamin-sensitive inhibitory junction potentials induced by a single pulse of EFS. The PACAP-induced relaxation of longitudinal muscle occurred with a concomitant decrease in intracellular Ca 2+ levels ([Ca 2+ ] i ). Tyrphostin 25 at 10 μ m and apamin at 1 μ m abolished these PACAP-induced responses. From these findings it is suggested that the activation of tyrosine kinase is involved in PACAP-induced relaxation of longitudinal muscle from rat distal colon, ‘upstream of’ the activation of apamin-sensitive K + channels.