Carbachol does not down-regulate substance P receptors in pancreatic acini

Area of Science:

• Gastroenterology
• Endocrinology
• Cell Signaling

Background:

• Previous studies indicated carbachol desensitizes pancreatic acini to CCK-8, bombesin, and itself, potentially via receptor downregulation.
• The effect of carbachol on substance P-induced responses and its receptors remained unexamined despite substance P not causing desensitization.

Purpose of the Study:

• To investigate the effect of carbachol on substance P-mediated amylase secretion and substance P receptor binding in guinea pig pancreatic acini.
• To compare the effects of carbachol on substance P signaling with its known effects on CCK-8 and bombesin signaling.

Main Methods:

• Dispersed guinea pig pancreatic acini were used to measure amylase secretion and radioligand binding assays.
• Substance P and cholecystokinin-octapeptide (CCK-8) were used as stimuli.
• Binding of 125I-substance P and 125I-CCK-8 to their respective receptors was assessed after incubation with or without carbachol.

Main Results:

• Substance P stimulated amylase secretion in a dose-dependent manner, with maximal effect at 10 nM and EC50 of 0.7 nM.
• Radioligand binding studies revealed a single class of substance P receptors with a Kd of 0.8 nM, correlating closely with the secretory response.
• Carbachol pre-incubation did not alter substance P-stimulated secretion or substance P receptor binding, but significantly reduced CCK-8 binding and CCK-8-stimulated secretion.

Conclusions:

• Guinea pig pancreatic acini possess functional substance P receptors that mediate amylase secretion.
• Carbachol does not desensitize the substance P signaling pathway or affect substance P receptor availability.
• These findings highlight a differential regulation of peptide hormone receptor signaling pathways in pancreatic acini by carbachol.