SOMATOSTATIN-MEDIATED INHIBITORY POSTSYNAPTIC POTENTIAL IN SYMPATHETICALLY DENERVATED GUINEA-PIG SUBMUCOSAL NEURONS

1. Intracellular recordings were made from submucosal neurones in guin ea-pig ileum. In some animals, the extrinsic (sympathetic) nerves to t he submucosal plexus were severed 5-7 days previously. The actions of somatostatin and somatostatin analogues on membrane potential, membran e current and inhibitory postsynaptic potentials (IPSPs) were examined . 2. Somatostatin, somatostatin(1-28), [D-Trp8]somatostatin and the so matostatin analogue CGP 23996 all produced equivalent maximum hyperpol arizations or outward currents; half-maximal concentrations (EC50 valu es) were 9-11 nm. The somatostatin analogue MK 678 had an EC50 of 0.9 nm. Extrinsic sympathectomy did not alter concentration-response relat ions for somatostatin or its analogues. 3. Somatostatin (> 100 nm) pro duced hyperpolarization or outward current that declined almost comple tely during superfusion for 2-4 min; decline of the somatostatin curre nt was exponential with a time constant of 30 s in the presence of 2 m um somatostatin. Desensitization was not altered by extrinsic denervat ion. 4. Recovery from desensitization was rapid and followed the time course of agonist wash-out. Forskolin, phorbol esters, dithiothreitol, hydrogen peroxide, concanavalin A, or reducing temperature from 35 to 29-degrees-C did not alter the time course, degree of, or recovery fr om desensitization. 5. The somatostatin-induced desensitization was of the homologous type; no cross-desensitization to opiate or alpha2-adr enoceptor agonists (which activate the same potassium conductance) occ urred. 6. Somatostatin desensitization did not alter the adrenergic IP SP seen in sympathetically innervated preparations but abolished the n on-adrenergic IPSP recorded from normal preparations and from preparat ions in which the extrinsic sympathetic nerve supply had been surgical ly removed. 7. The selective blockade of the non-adrenergic IPSP by th e homologous-type somatostatin desensitization characterized in the pr esent study provides strong support for the hypothesis that somatostat in is the neurotransmitter underlying the non-adrenergic IPSP in both normal and extrinsically denervated submucosal neurones.