Differences In The Expression Of Vpac2 Receptors And Adenylyl Cyclase V/Vi And Vip-Induced Camp Generation In Phasic And Tonic Smooth Muscles

The proximal stomach is characterized by its ability to maintain tone as compared to the distal stomach, which is phasic in nature and contracts transiently. In gastric muscle, the inhibitory transmitters VIP, PACAP and NO mediate relaxation. VIP and PACAP interact with VPAC2 receptors to stimulate adenylyl cyclase (AC) activity and cAMP formation. AIM To determine whether differences in the VPAC2/AC/cAMP pathway are related to tonic and phasic phenotype of smooth muscles in proximal and distal regions of the stomach, respectively. METHODS Expression of VPAC2 receptor and ACV/VI, the main isoforms(s) expressed in smooth muscle, are determined in muscle cells isolated separately from proximal and distal stomach by qRT-PCR and western blot. Stimulation of AC activity in response to VIP was measured as increase in cAMP formation in the presence of IBMX. RESULTS Expression of VPAC2 receptors and ACV/VI was significantly higher in muscle from distal stomach than from proximal stomach. Consistent with the higher expression of VPAC2 receptors and ACV/VI, VIP induced cAMP levels were significantly higher in muscle cells from distal stomach than muscle cells from proximal stomach. CONCLUSION Higher expression of VPAC2 receptors and ACV/VI, and greater generation of cAMP that mediate relaxation in muscle from distal stomach correlate with the phasic phenotype of muscle in distal stomach relative to proximal stomach.