Histamine H-2 receptor activated chloride conductance in myenteric neuronsfrom guinea pig small intestine

Whole cell perforated patch-clamp methods were used to investigate ionic me chanisms underlying histamine-evoked excitatory responses in small intestin al AH-type myenteric neurons. When physiological concentrations of Na+, Ca2 +, and Cl- were in the bathing medium, application of histamine significant ly increased total conductance as determined by stepping to 50 mV from a ho lding potential of -30 mV. The current reversed at a membrane potential of -30 +/- 5 (SE) mV and current-voltage relations exhibited outward rectifica tion. The reversal potential for the histamine-activated current was unchan ged by removal of Na+ and Ca2+ from the bathing medium. Reduction of Cl- fr om 155 mM to 55 mM suppressed the current when the neurons were in solution s with depleted Na+ and Ca2+. Current-voltage curves in solutions with redu ced Cl- were linear and the reversal potential was changed from -30 +/- 5 m V to 7 +/- 4 mV. Niflumic acid, but not anthracene-9-carboxylic acid (9-AC) nor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), suppressed the histamine-activated current. A membrane permeable analogue of cAMP evok ed currents similar to those activated by histamine. A selective histamine H-2 receptor agonist (dimaprit) mimicked the action of histamine and a sele ctive histamine H-2 receptor antagonist (cimetidine) blocked the conductanc e increase evoked by histamine, A selective adenosine A(1) receptor agonist (CCPA) reduced the histamine-activated current and a selective adenosine A (1) receptor antagonist (CPT) reversed the inhibitory action. The results s uggest that histamine acts at histamine H-2 receptors to increase Cl- condu ctance in AH-type enteric neurons. Cyclic AMP appears to be a second messen ger in the signal transduction process. Results with a selective adenosine A(1) receptor agonist and antagonist add to existing evidence for co-coupli ng of inhibitory adenosine A(1) receptors and histamine H-2 receptors to ad enylate cyclase in AH-type enteric neurons.