Abstract

The effects of putative sigma ligands and two neuropeptides on intestinal ion transport were evaluated in isolated sheets of whole mouse jejunum mounted in Ussing flux chambers. Serosal administration of neuropeptide Y (NPY), peptide YY (PYY), (+)-N-cyclopropylmethyl-N-methyl-1,4- diphenyl-1-ethyl-but-3-en-1-ylamine hydrochloride (JO 1784), di(ortho-tolyl)guanidine (DTG) and (+)- or (-)-N-allyl-normetazocine (NANM) produced concentration-related decreases in short-circuit current (Isc) without changes in tissue conductance. Although NPY and PYY were active in nanomolar concentrations, JO 1784, DTG and (+)- and (-)-NANM were active in micromolar concentrations; the rank order of potency in inhibiting Isc was PYY > NPY > JO 1784 = (-)-N- cyclopropylmethyl-N-methyl-1,4-diphenyl-1-ethyl-but-3-en-1-ylamine hydrochloride > DTG > (+)-NANM = (-)-NANM. Serosal application of tetrodotoxin effectively blocked the decrease in Isc associated with all of the ligands tested. The activity of the serosally applied ligands was blocked by prior application of chlorisondamine, a ganglionic blocker. The effects of JO 1784 and NPY were evaluated using antagonists of several receptor types. Although application of serosal haloperidol had no effect alone up to concentrations of 1 microM, this compound produced a rightward displacement in both the NPY and JO 1784 concentration-effect curves. In contrast, sulpiride, SCH-23390, naloxone, yohimbine and prazosin failed to antagonize the effects of NPY or JO 1784.(ABSTRACT TRUNCATED AT 250 WORDS)