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The role of vasoactive intestinal peptide (VIP) was investigated when mucosal stroking and 5-hydroxytryptamine (5-HT) were used to activate neural reflexes that stimulate chloride secretion in the guinea pig colon. Muscle-stripped segments of colon containing intact submucosal ganglia without myenteric ganglia were set up in modified flux chambers in order to record short-circuit current (Isc). Mucosal stroking with a brush for 1 s or a pulse of 5-HT (injection of 15 microliters of 100 microM 5-HT into 1.5 ml of mucosal solution) caused an increase in Isc that was reduced by the VIP antagonist, neurotensin6-11-VIP7-28, in a concentration-dependent manner. The Isc responses to mucosal stroking and a 5-HT pulse were reduced by 53% and 58%, respectively, by 2 microM neurotensin6-11-VIP7-28. The residual Isc response in the presence of neurotensin6-11-VIP7-28 was abolished by atropine. Blockade of 5-HT1P receptors on submucosal afferent neurons decreased Isc responses to stroking or a 5-HT pulse. The residual Isc response after 5-HT1P receptors were blocked was reduced by only 11-14% by neurotensin6-11-VIP7-28. In the presence of blockade of both 5-HT1P and VIP receptors, atropine abolished the Isc response to both stimuli. The observations suggest that the neural circuitry activated by stroking includes at least two independent pathways. One pathway contains VIP neurons which receive inputs directly or indirectly from 5-HT1P receptor-containing afferents. A second pathway involves muscarinic cholinergic transmission that is independent of 5-HT1P and VIP receptor activation.

The effect of vagotomy on the development of ECL cell tumours was analyzed during drug-induced hypergastrinemia in Mastomys natalensis, a rodent prone to develop ECL cell tumours. Untreated animals were compared with animals receiving the histamine2-receptor blocker loxtidine (LOX) and with animals subjected to unilateral subdiaphragmatic vagotomy prior to loxtidine treatment (VAG+LOX). Loxtidine (2g/l) was administered in drinking water for 48 weeks to allow multiple ECL cell carcinoids to develop. Plasma gastrin levels were increased in LOX animals (94 +/- 31 pmol/l) and in VAG+LOX animals (181 +/- 59 pmol/l) compared to controls (45 +/- 4 pmol/l). Corpus weight and oxyntic mucosal thickness was almost doubled in all loxtidine-treated animals and the density of mucosal endocrine cells was increased by 65% in the LOX group and by 135% in VAG+LOX animals. No significant differences in mucosal thickness and endocrine cell density were seen when denervated and intact parts of the stomach were compared. In the VAG+LOX animals endocrine cell neoplasia was seen in 60% and dysplasia in 40% of animals compared to 40% neoplasia, 45% dysplasia and 15% hyperplasia in LOX animals. The frequency of neoplastic and dysplastic lesions did not differ between denervated and intact parts of the stomach. Untreated animals showed no neoplastic or dysplastic lesions. It is concluded that unilateral vagotomy has no protective effect on the development of ECL-cell tumours in Mastomys during hypergastrinemia, as opposed to previous studies in the rat.