Histamine H(2) receptor activated chloride conductance in myenteric neurons from guinea pig small intestine.
Whole cell perforated patch-clamp methods were used to investigate ionic mechanisms underlying histamine-evoked excitatory responses in small intestinal AH-type myenteric neurons. When physiological concentrations of Na(+), Ca(2+), and Cl(-) were in the bathing medium, application of histamine significantly increased total conductance as determined by stepping to 50 mV from a holding potential of -30 mV. The current reversed at a membrane potential of -30 +/- 5 (SE) mV and current-voltage relations exhibited outward rectification. The reversal potential for the histamine-activated current was unchanged by removal of Na(+) and Ca(2+) from the bathing medium. Reduction of Cl(-) from 155 mM to 55 mM suppressed the current when the neurons were in solutions with depleted Na(+) and Ca(2+). Current-voltage curves in solutions with reduced Cl(-) were linear and the reversal potential was changed from -30 +/- 5 mV 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 evoked currents similar to those activated by histamine. A selective histamine H(2) receptor agonist (dimaprit) mimicked the action of histamine and a selective histamine H(2) receptor antagonist (cimetidine) blocked the conductance 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 suggest that histamine acts at histamine H(2) receptors to increase Cl(-) conductance in AH-type enteric neurons. Cyclic AMP appears to be a second messenger in the signal transduction process. Results with a selective adenosine A(1) receptor agonist and antagonist add to existing evidence for co-coupling of inhibitory adenosine A(1) receptors and histamine H(2) receptors to adenylate cyclase in AH-type enteric neurons.
Starodub
A M
AM
Department of Physiology, College of Medicine and Public Health, Ohio State University, Columbus, Ohio 43210-1218, USA.
Wood
J D
JD
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007421:Intestine, Small / Q000294:innervation*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009197:Myenteric Plexus / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D009544:Niflumic Acid / Q000494:pharmacology; D019899:Paracrine Communication / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D011970:Receptors, Histamine H2 / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D058906:Purinergic P1 Receptor Agonists; D011970:Receptors, Histamine H2; D013873:Thionucleotides; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; C053907:8-cyclopentyl-1,3-dimethylxanthine; C058394:2-chloro-N(6)cyclopentyladenosine; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D009544:Niflumic Acid; D006632:Histamine; D013806:Theophylline; D000242:Cyclic AMP; D000241:Adenosine; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D015056:1-Methyl-3-isobutylxanthine