Coordination of Cl- secretion and contraction by a histamine H2-receptor agonist in guinea pig distal colon

Abstract

Short-circuit current (Isc) was measured simultaneously with muscle tension recorded in the longitudinal or circumferential axis from strain-gauge transducers sutured to the serosal surface of whole thickness segments of distal colon from guinea pigs. Isc and the amplitude and frequency of small-amplitude phasic contractions were stable for several hours. The histamine H2-receptor agonist dimaprit (5-10 microM) evoked recurrent increases in Isc at a frequency of 0.32-0.37 cycles/min. Associated with each cyclical Isc response was an increase in muscle tension indicative of large-amplitude phasic contractions. Recurrent cycles of Isc and associated large-amplitude phasic contractions were abolished by 10 microM cimetidine. In the presence of dimaprit, severing the neural connections between the myenteric and submucosal plexuses abolished the large-amplitude phasic contractions but not cyclical Isc. The results suggest that coordination of cyclical secretion and large-amplitude contraction during chronic activation of histamine H2 receptors requires intact neural connections between the submucosal and myenteric plexuses. The findings provide potential mechanisms to explain altered motility and ion transport during inflammatory diseases or allergic responses to food antigens.