Ontogeny of adenosine receptors in the longitudinal muscle and muscularis mucosae of the rat distal colon

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 1999-02, Vol.359 (2), p.140-146
• Main Authors: Peachey, J A, Hourani, S M, Kitchen, I
• Format: Article
• Language: English
• Subjects: Adenosine - analogs & derivatives; Adenosine - metabolism; Adenosine - pharmacology; Adenosine-5'-(N-ethylcarboxamide) - pharmacology; Aging - metabolism; Animals; Autoradiography; Binding Sites; Binding, Competitive; Colon - growth & development; Colon - metabolism; Colon - physiology; Male; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle Development; Muscle, Smooth - growth & development; Muscle, Smooth - metabolism; Muscle, Smooth - physiology; Radioligand Assay; Rats; Rats, Wistar; Receptors, Purinergic P1 - metabolism; Subcellular Fractions - metabolism; Vasodilator Agents - pharmacology; Xanthines - metabolism; Xanthines - pharmacology
• ISSN: 0028-1298
• DOI: 10.1007/pl00005333

The development of adenosine A1 and A2B receptors on the longitudinal muscle and muscularis mucosae of the neonatal rat distal colon has been investigated using homogenate binding, quantitative autoradiography and functional studies. In homogenate binding studies 1,3-[3H]-dipropyl-8-cyclopentylxanthine ([3H]DPCPX) bound with high affinity to A1 receptors in the muscularis mucosae and intact colon from rats aged 10, 15, 20, 25 and 30 days. The affinity of [3H]DPCPX was similar to that in the adult at all ages, but the density of binding sites was higher in the neonatal tissues. Quantitative autoradiography showed a higher density of [3H]DPCPX binding sites in the longitudinal muscle than in the muscularis mucosae at all ages studied (day 10 to adult), and this binding was concentration-dependently displaced by N6-cyclopentyladenosine (CPA). In functional studies the longitudinal muscle relaxed in response to 5'-N-ethylcarboxamidoadenosine (NECA) and CPA at all ages studied (15-30 days), NECA being more potent than CPA. The potency of NECA remained constant and it was antagonised by 1 microM DPCPX at all ages with pA2-values consistent with activation of A2 receptors. The inactivity of 2-[p-(carboxyethyl)-phenylethylamino]-5'-N-ethylcarboxamidoadenosi ne (CGS 21680) indicated that the A2 receptors were of the A2B subtype. The muscularis mucosae contracted in response to CPA at all ages studied (day 15 to adult) and the antagonism by DPCPX (10 nM) were consistent with activation of A1 receptors. In conclusion, binding, autoradiographic and functional studies identified A1 receptors on the rat colon muscularis mucosae at all ages studied. However, while binding and autoradiographic localisation showed the presence of A1 receptors in the longitudinal muscle at all ages studied, functional data only revealed the presence of A2B receptors.