Characterization of the VIP- and secretin-stimulated adenylate cyclase system from human lung.
The response of a crude particulate adenylate cyclase preparation from surgically removed human lung to guanine nucleotides, sodium fluoride, beta-adrenergic agonists, prostaglandins, vasoactive intestinal peptide (VIP), secretin, and [Val5]secretin was investigated. The enzyme activity increased 5, 10, and 9-fold, respectively, with GTP, Gpp(NH)p, and sodium fluoride. This activity was stimulated (in the presence as well as in the absence of added GTP) by D,L-isoproterenol, L-epinephrine and L-norepinephrine, the relative potency of these agonists being compatible with the existence of beta-adrenoceptors of the beta2 subtype. Prostaglandins E1 and E2, but not PGF1alpha and PGF2alpha, stimulated the enzyme, PGE1 being at least 10 times more potent than PGE2. The biphasic pattern of stimulation of the same adenylate cyclase activity by VIP suggested the presence of high- and low-affinity VIP receptors coupled to the enzyme. This stimulation by VIP was not inhibited by secretin-(7-27). The stimulation of adenylate cyclase by secretin and [Val5]secretin was also biphasic, suggesting the coexistence of high- and low-affinity secretin receptors. Secretin-(7-27) was able to inhibit completely the secretin stimulation acting through high-affinity secretin receptors but exerted no effect on the stimulation operating through low-affinity secretin receptors, which might indicate that the latter receptors were in fact "VIP-preferring receptors". [Val5]secretin was also used to differentiate these peptide receptors, since its properties were more VIP-like than those of secretin.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D004789:Enzyme Activation; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D006150:Guanine Nucleotides / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011453:Prostaglandins / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects*; D018005:Receptors, Vasoactive Intestinal Peptide; D012633:Secretin / Q000494:pharmacology*; D012969:Sodium Fluoride / Q000494:pharmacology; D013268:Stimulation, Chemical; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D005768:Gastrointestinal Hormones; D006150:Guanine Nucleotides; D011453:Prostaglandins; D011956:Receptors, Cell Surface; D018005:Receptors, Vasoactive Intestinal Peptide; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D012969:Sodium Fluoride; D000262:Adenylyl Cyclases