Activation of Histamine Receptors is Associated with Amylase Secretion and Calcium Mobilization in Guinea-Pig Pancreatic Acinar Cells

Abstract

An investigation was made on the effects of histamine and related receptor agonists and antagonists on amylase secretion and Ca²⁺ mobilization in isolated guinea pig pancreatic segments and acinar cells. The effect of acetylcholine (ACh) was examined for comparison. Histamine evoked marked dose-dependent increases in amylase secretion and small changes in 45Ca²⁺ efflux, 45Ca²⁺ influx and intracellular free Ca²⁺ concentration [Ca²⁺]i, compared to much larger responses obtained with ACh. The H₁ receptor agonist 2-thiazolyl-ethylamine (2-TEA) elicited a small increase in amylase secretion, whereas the H₂ receptor agonist dimaprit had little or no effect. Similarly, 2-TEA evoked only small increases in Ca²⁺ mobilization, whereas dimaprit had no detectable effect. The H₂ receptor antagonist oxmetidine also stimulated amylase output in a dose-dependent manner, similar in magnitude to histamine, whereas the H₁ receptor antagonist chlorpheniramine (CPR) was only effective as a secretagogue at 10^–2 M The H₁ antagonist also completely abolished the secretory responses of 2-TEA and markedly reduced the histamine-induced amylase secretion. The results demonstrate the involvement of histamine receptors in the control of amylase secretion and Ca²⁺ mobilization in guinea pig pancreatic acinar cells.

Histaminergic modulation of hormonal control in the exocrine guineapig pancreas

“…A. Pariente significant rise in enzyme secretion. Similar findings have been obtained by us in guinea-pig pancreatic segments [8,14] and lobules [15]. Furthermore, Lorenz et al [12] showed that the dog pancreatic juice obtained by stimulation by secretin and pilocarpine contains histamine in a high concentration which is constant during the whole secretion period.…”

“…Although Harvey and Owen [24] demonstrated vascular effects for histamine, it is worth noting that there was no sustained disturbance in blood pressure during the experiments. Moreover, previous studies have demonstrated that histamine can elicit an increase in amylase secretion from pancreatic segments [14], lobules [3,15] and acinar cells [8]. Nevertheless, we cannot reject that a part of the effects observed in this study may be due to changes in the mesenteric circulation.…”

“…Pancreatic tissues have an average histamine content of 1.3 gg/g; a value which is three times the histamine content of skeletal muscle and one-eighth the content of stomach fundus [3]. Previous studies on exocrine pancreatic secretion have demonstrated that histamine can act as a secretagogue in both the anaesthetised dog and rabbit [5-7, 12, 13] as well as on the rabbit and guinea pig pancreas "in vitro" [3,8,14,15]. The present study has demonstrated that the paracrine agent histamine can also elicit an increase on exocrine pancreatic secretion in anaesthetised guinea pig.…”

The physiological role of histamine in the exocrine pancreas

“…In isolated guinea pig pancreatic segments, the H 2 receptor antagonist, oxmetidine stimulated amylase secretion in a dose-dependent manner, similar in magnitude to histamine whereas the H 1 receptor antagonist, chlorpheniramine was only effective at a pharmacological concentration of 10 ¹2 M [40]. In both the anaesthetized rabbit [35] and isolated guinea pig segments [40], application of selective H 1 receptor agonist, 2-thiazolyl-ethylamine resulted in marked increases in exocrine pancreatic secretion whereas the selective H 2 agonist, dimaprit had little or no effect.…”

“…Histamine can stimulate pancreatic juice secretion in the isolated dog pancreas [31], the anaesthetized dog [32,33], rabbit and guinea-pig [23,[34][35][36] but it is less effective as a secretagogue in the anaesthetized rat [37] and conscious dog [38]. In the in vitro pancreatic lobules of rabbit [28], segments of guinea pig [39,40] and rat [41] histamine can evoke marked increases in amylase secretion. Similarly, in guinea pig pancreatic acini the paracrine hormone can stimulate amylase output in a dose-dependent manner with maximal effect at 10 ¹3 M [30,42].…”