Synergistic augmentation of rhythmic myogenic contractions of human stomach by arginine vasopressin and adrenaline: Implications for the induction of nausea

• Published in: British journal of pharmacology Vol. 179; no. 24; pp. 5305 - 5322
• Main Authors: Makwana, Raj, Crawley, Ellie, Straface, Marilisa, Palmer, Alexandra, Gharibans, Armen, Devalia, Kalpana, Loy, John, O'Grady, Greg, Andrews, Paul L. R., Sanger, Gareth J.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.12.2022; John Wiley and Sons Inc
• Subjects: adrenaline; Adrenergic receptors; arginine vasopressin; Arginine Vasopressin - pharmacology; Argipressin; Argipressin receptors; Epinephrine; Epinephrine - pharmacology; human; Humans; Immunofluorescence; Interstitial cells; Interstitial cells of Cajal; Muscle Contraction; Nausea; Oxytocin; Receptors, Adrenergic, beta; Rhythms; Stomach; Vasopressin; Vasopressins; arginine vasopressin; stomach; adrenaline; human; interstitial cells of Cajal; nausea
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/bph.15943

Background and Purpose Nausea is associated with the hormonal secretion of vasopressin and adrenaline, although their actions in inducing nausea is poorly understood. Here, we have investigated their actions on human stomach muscle. Experimental Approach Muscle strips were suspended in tissue baths and neuronal‐/non‐neuronally‐mediated contractions were measured. Custom software analysed eight motility parameters defining spontaneous phasic non‐neuronally mediated contractions. Receptor distributions were assessed by qPCR and immunofluorescence. Key Results V1A receptors and α1‐adrenoceptors were located on muscle as well as interstitial cells of Cajal (ICCs). Myogenic contractions of human proximal and distal stomach (respectively, 2.6 ± 0.1 and 2.7 ± 0.0 per minute; n = 44) were larger in the distal area (1.1 ± 0.1 and 5.0 ± 0.1 mN), developing relatively slowly (proximal) or rapidly (distal). Vasopressin caused tonic (proximal) or short‐lived (distal) increases in muscle tone and increased myogenic contraction amplitude, frequency and rate (acting at V1A receptors; thresholds 10−11–10−10 M); by contrast, cholinergically mediated contractions were unaffected. Oxytocin acted similarly to vasopressin but less potently, at OT receptors). Adrenaline increased (10−10–10−5 M; α1‐adrenoceptors) and decreased (≥10−6 M; β‐adrenoceptors) muscle tone and enhanced/reduced myogenic contractions. Cholinergically mediated contractions were reduced (α2‐adrenoceptors). Combined, vasopressin (10−9 M) and adrenaline (10−8 M) increased muscle tone and phasic myogenic activity in a synergistic manner. Conclusions and Implications Vasopressin and adrenaline increased human gastric tone and myogenic contraction amplitude, rate of contraction and frequency. In combination, their actions were further increased in a synergistic manner. Such activity may promote nausea.