A pharmacological study of some relaxation processes in the rat oesophageal tunica muscularis mucosae

Akbarali, Hamid I. (1987) A pharmacological study of some relaxation processes in the rat oesophageal tunica muscularis mucosae. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

This thesis deals with pharmacological properties of rat oesophageal smooth muscle, viz. the tunica muscularis mucosae (TMM). Although the TMM contains the bulk of smooth muscle of the rodent oesophagus, its function is not fully understood. However, recent evidence supports an active role for the TMM in oesophageal motility. Present concepts of the processes involved in oesophageal peristalsis have emphasised the importance of neural inhibitory mechanisms in the smooth muscle layer of the oesophagus. The present study was thus chiefly concerned with relaxation responses of the TMM. -- The presence of a submucous ganglionated plexus in the isolated TMM was demonstrated by histological examination. The nerve plexus was found to contain acetyl- and butryl-cholinesterases and various peptide immunoreactive nerve fibres such as vasoactive intestinal peptide and calcitoningene related peptide. Adrenergic innervation was sparse in the proximal and supradiaphramatic portion of the TMM; serotonin was observed to be localised to mast cells but not to nervous elements. -- In the presence of cholinoceptor-induced tone relaxation responses were elicited in the TMM by field-stimulation and by stimulation of the vagus provided excitatory responses to electrical stimulation were blocked. Relaxations were also examined to pharmacological agents. -- Field-stimulation of the isolated TMM produced both a tetrodotoxin (TTX) -sensitive and TTX-insensitive relaxation. The former was sensitive to guanethidine in the distal but not in the proximal segment. The TTX-insensitive response was unaffected by a variety of pharmacological agents and not abolished by cold storage. It was however diminished by cooling and by calcium antagonists. This form of relaxation was characterised as purely myogenic and a consequence of K⁺ efflux activated by calcium entry through potential-operated channels following field-stimulation. Vagally-stimulated relaxations in the whole oesophagus preparation were insensitive to hexamethonium. Relaxations to pharmacological agents such as 5HT and A23187 were found to have a regional gradient with the proximal TMM segments being more responsive than the distal segments. -- This study demonstrates that the isolated TMM with its attached submucous plexus is capable of relaxing to both electrical and pharmacological stimuli.

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