BETA-ADRENERGIC REGULATION OF GAP-JUNCTIONAL INTERCELLULAR COMMUNICATION IN CULTURED RABBIT GASTRIC EPITHELIAL-CELLS

The effect of a beta-adrenergic agonist, isoproterenol, on gap-junctio nal intercellular communication (GJIC) and intracellular cyclic AMP (c AMP) content was investigated in cultured rabbit gastric epithelial ce lls. Isoproterenol rapidly enhanced GJIC determined by the Lucifer yel low transfer at 10(-6) and 10(-5) M but the effect at 10(-6) M was var iable. The enhancement of GJIC by 10(-5) M isoproterenol, which disapp eared within 10 or 30 min, was inhibited by a beta blocker, propranolo l. Isoproterenol (10(-6) M) greatly increased cAMP at 5 min and much m ore so at 20 min after its addition. Colforsin (also known as forskoli n) and 3-isobutyl-1-methylxanthine (IBMX) enhanced GJIC until 16 and 2 0 min after their addition, respectively. Both colforsin and IBMX incr eased the cAMP content by a lesser extent than 10(-6) M isoproterenol. Isoproterenol (10(-5) M) inhibited the GJIC enhanced by colforsin or IBMX. Propranolol abolished the inhibition of GJIC by isoproterenol in the presence of IBMX. Both amiloride, an inhibitor of the Na+/H+ exch anger, and nigericin, a K+/H+ antiporter, inhibited the GJIC enhanced by isoproterenol, IBMX, colforsin and irsogladine. An inhibitor of cAM P-dependent protein kinase A, H-89 propenyl)-amino)-ethyl]-5-isoquinol inesulfonamide) abolished the enhancement of GJlC by colforsin and IBM X but did not abolish that by isoproterenol. From these results, stimu lation of beta-adrenergic receptors by isoproterenol seems to act in t wo opposite directions on GJIC as follows: 1) facilitation of GJIC by the activation of the Na+/H+ exchanger, which elevates intracellular p H, independent of cAMP production in resting cells; and 2) inhibition of GJIC, which has already been activated. In addition, the activation of the Na+/H+ exchanger may play a crucial role in facilitating GJIC.