NITRIC-OXIDE SYNTHASE IN NEURONS OF THE HUMAN GALLBLADDER AND ITS COLOCALIZATION WITH NEUROPEPTIDES

The distributions of nerve cells and fibres chat are immunoreactive fo r nitric oxide synthase (NOS) have been investigated in the human gall -bladder. In addition, the colocalization of NOS immunoreactivity (IR) with neuropeptide Y (NPY), pituitary adenylyl cyclase activating pept ide (PACAP), somatostatin (SOM), substance P (SP), tyrosine hydroxylas e (TH) and vasoactive intestinal peptide (VIP)-IR was determined. Nitr ic oxide synthase-IR nerve cell bodies comprised 13 and 30% of nerve c ells in ganglia of the fibromuscular and subepithelial layers, respect ively. To determine these percentages, neuron-specific enolase-IR was used as a marker for all nerve cells. Although SOM- and VIP-IR nerve c ell bodies were found in both ganglia, they rarely contained NOS-IR. I n the fibromuscular layer, NOS-IR nerve fibres were abundant and most PACAP-, SOM- and VIP-IR fibres and many NPY-IR fibres were also NOS po sitive. No colocalization was observed between NOS- and SP- or TH-IR. In the mucosal layer, moderate numbers of NOS-IR fibres were found and the degree of colocalization of NOS-IR with each of NPY-, PACAP-, SOM -, SP- and VIP-IR were as follows: PACAP and NPY >VIP >SOM and SP. Nit ric oxide synthase and TH were not colocalized in mucosal fibres. Thes e results suggest that nerve fibres in the fibromuscular layer in the human gall-bladder with the chemical coding NOS/NPY/PACAP/SOM/VIP are axons of inhibitory motor neurons. Nitric oxide synthase-IR fibres in the mucosal layer that contained NPY, PACAP, SOM, SP and VIP with vari ous degrees of colocalization probably contribute to the control of ep ithelial secretion or absorption.