Postnatal changes in receptor-mediated rabbit gastric smooth muscle relaxation.

The aims of this study were to identify mediators of relaxation in rabbit proximal gastric circular smooth muscle and to assess age-dependent changes in tissue response. Vasoactive intestinal peptide (VIP), adenosine, and norepinephrine induced tetrodotoxin-insensitive, concentration-dependent relaxation in bethanechol-precontracted (3 microM) gastric muscle strips from newborns and weanlings. Maximally effective concentrations of 10 microM VIP induced complete relaxation in newborns, but only 30% relaxation in weanlings (p < 0.01). Maximally effective concentrations of adenosine induced complete relaxation at both ages. Adenosine (ED50 3 microM) was more potent than adenosine triphosphate, indicating the presence of P1 purinergic receptors. In newborns norepinephrine induced complete relaxation (ED50 0.5 microM). The response to norepinephrine changed in age-dependent increments from relaxation in newborns to strong contraction in weanlings. In weanlings phentolamine inhibited norepinephrine-stimulated contraction, revealing persistent propranolol-sensitive relaxation. Tetrodotoxin and atropine had no effect on norepinephrine-stimulated contraction. In summary, in rabbit gastric circular smooth muscle: (1) VIP, adenosine, and norepinephrine induce relaxation; (2) VIP loses efficacy with age; (3) there is a beta-adrenergic receptor mediating relaxation in the newborn which persists, and (4) an alpha-adrenergic receptor mediating contraction emerges early in postnatal life. Age-dependent changes in response to VIP and norepinephrine may contribute to the postnatal maturation of the gastric motility.