THE RAT HOMOLOG OF THE BOVINE ALPHA(1C)-ADRENERGIC RECEPTOR SHOWS THEPHARMACOLOGICAL PROPERTIES OF THE CLASSICAL ALPHA(1A) SUBTYPE

The cDNA for the rat alpha(1c)-adrenergic receptor (AR) has been clone d using a probe derived from the bovine alpha(1c)-AR sequence. Clone r B7a has a 2.6-kilobase insert with a 1390-base pair open reading frame and encodes a receptor of 466 amino acids. The cloned receptor has 91 % amino acid identity with the bovine cute AR. The rat alpha(1c)-AR mR NA was detected in tissues known to be enriched for the alpha(1A)-AR s ubtyper including vas deferens, heart, kidney, and hippocampus. Rat al pha(1c)-AR mRNA was absent from liver and spleen when assayed by North ern blot analyses and RNase protection assays. In COS-7 cells transfec ted with cDNAs encoding the three rat alpha(1)-ARs, WB-4101 and benoxa thian had similar binding affinities for the alpha(1a/d)-AR and the al pha(1c)-AR and 10-fold lower affinities for the alpha(1b)-AR. The affi nity of 5-methylurapidil was found to be 10- and 30-fold higher at the alpha(1c)-AR than at the alpha(1a/d)- and alpha(1b)-ARs, respectively . (S)-(+)-Niguldipine was found to have high affinity for the rat alph a(1c)-AR, with 42- and 22-fold lower affinity at the alpha(1a/d)- and alpha(1b)-ARs, respectively. Treatment of intact transfected COS-7 cel ls with chlorethylclonidine resulted in the inactivation of 19% of the alpha(1c)-ARs, in contrast to 72% and 85% inactivation of the alpha(1 a/d)- and alpha(1b)-ARs, respectively. Similarly to the other two alph a(1)-ARs, the rat alpha(1c)-AR is coupled to the activation of phospho lipase C. Our data suggest that the rat alpha(1c)-AR cDNA encodes an a lpha(1)-AR with the pharmacological properties previously defined for the alpha(1A) subtype found in tissues.