The effects of histamine on the gallbladder and exocrine pancreas of the guinea-pig

Abstract

In the mammalian gastrointestinal tract histamine has multiple functions including contraction of smooth muscle and secretion of gastric acid. This study investigated the secretory and contractile actions of histamine on the exocrine pancreas and gallbladder of the guinea-pig respectively. Application of histamine to the isolated gallbladder strip elicited contraction Of the tissue. This net effect of histamine was subsequently found to be a result of stimulation of two of the major classes of histamine receptor, H I and H2. Application of histamine H1-receptor agonists and antagonists confirmed that the contractile effect in this preparation was histamine H1-receptor mediated. Stimulation of the histamine H2-receptor in this preparation with specific agonists and antagonists revealed an inhibitory or relaxatory component. Stimulation of the third major subclass
of histamine receptor, H3, with specific agonists and antagonists over a background of electrical field stimulation revealed no attenuation of the contractile response. This may have been due to the absence of the receptor in this preparation, or
alternatively, a lack of sensitivity in the experimental conditions which would enable characterisation of the receptor. Histamine failed to elicit significant amylase secretion from pancreatic segments. However, the use of histamine agonists and antagonists demonstrated that histamine may be able to elicit secretion at high concentrations. In addition, histamine was able to attenuate secretion from both the in-viva and in-vitro pancreas via stimulation of the histamine H3-receptor. This novel finding was shown to involve the inhibition of cholinergic neurotransmitter release. The possible physiological source of histamine was identified with histological methods. Mast cells containing histamine were identified for the first time in these tissues.
Immunoreactivity to neural peptides revealed possible links between nerves and mast cells particularly in the gallbladder. Histamine may prove to be an important physiological mediator between nerves and effector tissue in the exocrine pancreas.